Eunkyue Park - Academia.edu (original) (raw)

Papers by Eunkyue Park

Regulation of nitric oxide induced by mycobacterial lipoarabinomannan in murine macrophages: Effects of interferon-β and taurine-chloramine

International Journal of Leprosy and Other Mycobacterial Diseases, 2000

Inflammatory mediators are inhibited by a taurine metabolite in CpG oligodeoxynucleotide and IFN-r activated macrophage cell line

Journal of Drugs in Dermatology Jdd, May 1, 2013

Taurine plays an important role in brain and retinal development, and has an antiinflammatory and... more Taurine plays an important role in brain and retinal development, and has an antiinflammatory and antioxidant function. Taurine chloramine (Tau-Cl) is produced in polymorphonuclear leukocytes via the myeloperoxidase/halide system. We previously demonstrated that Tau-Cl inhibits the production of nitric oxide (NO) and TNF-α in human and murine macrophages activated with IFN-γ in combination with individual Toll-like receptor (TLR) ligands including those for TLR2 and/or TLR4. In the current study, we further explored the effects of Tau-Cl in RAW 264.7 cells stimulated with the TLR9 ligand CpG oligodeoxynucleotide (ODN). Specifically, we examined the effect of CpG ODN plus IFN-γ on the production of NO and TNF-α, and the effect of Tau-Cl on this process. Our findings show that CpG ODN plus IFN-γ-activated RAW 264.7 cells secrete high levels of NO and TNF-α, and that Tau-Cl (0.8 mM) inhibits this effect in a dose-dependent manner, more potently inhibiting the production of NO (99% inhibition) than that of TNF-α (48% inhibition). Nitric oxide synthase (iNOS) protein was also induced by CpG ODN plus IFN-γ, and was also inhibited by Tau-Cl. Furthermore, while CpG ODN plus IFN-γ induced TNF-α and iNOS mRNAs, Tau-Cl transiently suppressed this effect. Taurine itself had no effects on any of these processes. Our findings in a macrophage cell line demonstrate that Tau-Cl inhibits proinflammatory mediators resulting from TLR9 activation, and have implications for the utility of Tau-Cl in scenarios where such activation is deleterious such as in autoimmune conditions or infections in which overwhelming inflammation may occur. CpG ODNs and Tau-Cl both have potential for topical treatment of autoimmune conditions, including psoriasis, vitiligo, and alopecia areata. As CpG ODNs may, under some conditions, up-regulate Tregs, addition of Tau-Cl to CpG ODN topical formulations has potential for improving cancer immunotherapy.

Deficient Tumor Necrosis Factor-α Production in Lipoarabinomannan Activated Macrophages from Toll-like Receptor-4 Deficient Mice: Implication for Mycobacterial Susceptibility

International Journal of Leprosy and Other Mycobacterial Diseases, 2003

Taurine Protects Rat Bronchioles from Acute Ozone-Induced Lung Inflammation and Hyperplasia

Experimental Lung Research, 1995

Ozone is a potent respiratory irritant known to induce lung injury in humans and experimental ani... more Ozone is a potent respiratory irritant known to induce lung injury in humans and experimental animals. The present studies determined if ozone-induced lung inflammation was modified by pretreatment of animals with taurine, a detoxifying antioxidant. Rats were pretreated for 10 days with 5% taurine in their drinking water (controls received water only) prior to exposure to 2 ppm ozone for 3 h. At 2, 6, 12, 24, 48, and 72 h after ozone exposure, rats were anesthetized and the lungs were perfusion-fixed for histopathologic evaluation. An additional group of rats was used to examine bronchoalveolar lavage cell counts and hydroxyproline levels. A count of bronchoalveolar lavage cells 48 h after ozone exposure showed significantly fewer total inflammatory cells and fewer polymorphonuclear leukocytes accompanied by a reduction in hydroxyproline in the lavage fluid of ozone-exposed rats pretreated with taurine compared to rats that did not receive taurine. Light microscopy revealed an inflammatory cell infiltrate in the lungs of rats exposed to ozone. This was followed by focal hyperplasia in the terminal and respiratory bronchioles. Rats pretreated with taurine and then exposed to ozone showed none of these alterations. In addition, although there was a significant reduction in cell proliferation as measured by DNA precursor incorporation in the lungs of rats pretreated with taurine prior to ozone exposure compared to unsupplemented rats, the distribution of labeled cells was the same in taurine supplemented and unsupplemented groups. Also, significantly higher levels of taurine were found in the plasma, whole blood, and lavage fluid of rats pretreated with dietary taurine compared to rats that received water only. The results suggest that supplemental taurine protects rat lung epithelium from acute ozone-induced lung inflammation and hyperplasia.

Effect of thalidomide on nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells

Journal of Drugs in Dermatology Jdd, Apr 1, 2010

Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 ... more Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 (T helper 1) immunity measured by increased IL-2 (Interleukin-2) and gamma interferon. The authors have assessed the effect of thalidomide and analogues, di- and tri-thiothalidomide, on a lipopolysaccharide (LPS) activated macrophage cell line (RAW 246.7 cells). The authors' findings showed that nitric oxide (NO) was significantly inhibited by thalidomide (15%) and its analogues (di-thiothalidomide; 15%, tri-thiothalidomide; 32%). The proinflammatory molecules TNF-alpha (tumor necrosis factor-alpha) and IL-6 were not significantly inhibited. Pretreatment with thalidomide and analogues before activation was not different from simultaneous treatment. Inhibition of inducible nitric oxide synthase (iNOS) may prove to be an important target for the anti-inflammatory and anti-cancer effects of thalidomide and related immunomodulatory drugs (IMiDs).

Taurine protects against oxidant-induced lung injury: possible mechanism(s) of action

Advances in Experimental Medicine and Biology, Feb 1, 1994

It is thought that oxidant-induced tissue damage is not a direct effect of the oxidant per se, bu... more It is thought that oxidant-induced tissue damage is not a direct effect of the oxidant per se, but rather results from the inflammatory response that occurs thereafter. As a result of inflammation following oxidant exposure, there are neutrophils, monocytes, and macrophages with myeloperoxidase-H2O2-halide activity in the lung. Leukocytes and especially neutrophils contain high intracellular concentrations (22-50mM) of taurine (6, 8, 11, 20). Taurine acts as a trap for toxic hypochlorous acid (HOCl) and forms the less reactive metabolite, N-chlorotaurine (5-6). Thus, the biological activity of halide-dependent myeloperoxidase may be regulated by endogenous taurine. Although taurine had no effect in the present study, polymorphonuclear leukocytes have an active myeloperoxidase system capable of producing N-chlorotaurine (9, 19) and would be present at the site of inflammation in oxidant-exposed lungs. Our data suggest that taurine via N-chlorotaurine formation may protect the lung from oxidant injury, at least in part, by inhibiting production of nitrite and TNF-alpha. Moreover, lavage cells isolated from rats pretreated with taurine and exposed to O3 have a significant decrease in the production of nitrite and TNF-alpha, compared with lavage cells from rats exposed to O3 without taurine supplementation (preliminary studies). Both the concentration of taurine and the effects of N-chlorotaurine strengthen the potential impact of this chlorinated amine in vivo. N-Chlorotaurine may protect against oxidant-induced lung injury by inhibiting production of nitrite and the release of TNF-alpha which are both known to be directly linked to tissue injury.

Neurochemical Research, 2004

Taurine is a semiessential amino acid that is not incorporated into proteins. In mammalian tissue... more Taurine is a semiessential amino acid that is not incorporated into proteins. In mammalian tissues, taurine is ubiquitous and is the most abundant free amino acid in the heart, retina, skeletal muscle, and leukocytes. Taurine reaches up to 50 mM concentration in leukocytes. Taurine has been shown to be tissue-protective in many models of oxidant-induced injury. One possibility is that taurine reacts with HOCl, produced by the myeloperoxidase (MPO) pathway, to produce the more stable but less toxic taurine chloramine (Tau-Cl). However, data from several laboratories demonstrate that Tau-Cl is a powerful regulator of the immune system. Specifically, Tau-Cl has been shown to downregulate the production of proinflammatory mediators in both rodent and human leukocytes. Recent molecular studies on the function of taurine provide evidence that taurine is a constituent of biological macromolecules. Specifically, two novel taurine-containing modified uridines have been found in both human and bovine mitrochondria. In studies on mechanism of action, Tau-Cl inhibits the activation of NFB, a potent signal transducer for inflammatory cytokines, by oxidation of IB␣ at methionine 45 . Taurine transporter knockout mice show reduced taurine, reduced fertility, and loss of vision resulting from severe retinal degeneration, which was found to be due to apoptosis. Apoptosis induced by amino chloramines is a current and important finding because oxidants derived from leukocytes play a key role in killing pathogens. The fundamental importance of taurine in adaptive and acquired immunity will be revealed using genetic manipulation.

International Immunopharmacology, May 1, 2009

Taurine has been shown to protect against lung injury induced by various oxidants including ozone... more Taurine has been shown to protect against lung injury induced by various oxidants including ozone, nitrogen dioxide, amiodarone, and paraquat and to protect against bleomycin-induced lung injury in combination with niacin. In this study, Spraque-Dawley rats were treated with 5% taurine in the drinking water for 10 days prior to bleomycin instillation. Fibrosis in the rats pretreated with taurine (BT) was absent, along with fewer inflammatory infiltrates compared to the untreated rats (BW). A significant decrease in the number of PMNs and a decrease in hydroxyproline levels were found in the bronchoalveolar lavage fluid in the BT group compared to the BW group. By immunohistochemical staining, inducible nitric oxide synthase was evident in the lungs of bleomycintreated rats, and minimal when rats were treated with taurine. Tumor necrosis factor-alpha (TNF-α) as measured by immunohistochemical staining, was present in lungs of both taurine-treated and untreated rats, but was more abundant in the BW group compared to the BT group. In addition, decreased ICAM presentation was detected by EM immunogold staining in the BT group compared to the BW group. These data demonstrate that rats pretreated with 5% taurine in their drinking water prior to bleomycin instillation are protected from fibrosis, inflammatory infiltrates, as well as nitric oxide and TNF-α production, which are hallmarks of bleomycin lung injury.

Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo

Amino acids, Jan 20, 2015

The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mou... more The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mouse are not able to synthesize hypotaurine/taurine by the cysteine/cysteine sulfinate pathway and have very low tissue taurine levels. These mice provide excellent models for studying the effects of taurine on biological processes. Using these mouse models, we identified betaine:homocysteine methyltransferase (BHMT) as a protein whose in vivo expression is robustly regulated by taurine. BHMT levels are low in liver of both Cdo1-null and Csad-null mice, but are restored to wild-type levels by dietary taurine supplementation. A lack of BHMT activity was indicated by an increase in the hepatic betaine level. In contrast to observations in liver of Cdo1-null and Csad-null mice, BHMT was not affected by taurine supplementation of primary hepatocytes from these mice. Likewise, CSAD abundance was not affected by taurine supplementation of primary hepatocytes, although it was robustly upregulated...

Taurine chloramine inhibits the production of superoxide anion, IL-6 and IL-8 in activated human polymorphonuclear leukocytes

Advances in experimental medicine and biology, 1998

Search by Subject Search using Medical Subject Headings (< b> MeSH</b&gt... more Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.

A novel cysteine sulfinic Acid decarboxylase knock-out mouse: comparison between newborn and weanling mice

Advances in experimental medicine and biology, 2015

Effect of thalidomide on nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells

Journal of drugs in dermatology : JDD, 2010

Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 ... more Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 (T helper 1) immunity measured by increased IL-2 (Interleukin-2) and gamma interferon. The authors have assessed the effect of thalidomide and analogues, di- and tri-thiothalidomide, on a lipopolysaccharide (LPS) activated macrophage cell line (RAW 246.7 cells). The authors' findings showed that nitric oxide (NO) was significantly inhibited by thalidomide (15%) and its analogues (di-thiothalidomide; 15%, tri-thiothalidomide; 32%). The proinflammatory molecules TNF-alpha (tumor necrosis factor-alpha) and IL-6 were not significantly inhibited. Pretreatment with thalidomide and analogues before activation was not different from simultaneous treatment. Inhibition of inducible nitric oxide synthase (iNOS) may prove to be an important target for the anti-inflammatory and anti-cancer effects of thalidomide and related immunomodulatory drugs (IMiDs).

Taurine chloramine attenuates the hydrolytic activity of matrix metalloproteinase-9 in LPS-activated murine peritoneal macrophages

Advances in experimental medicine and biology, 2000

The production of superoxide anion and nitric oxide by cultured murine leukocytes and the accumulation of TNF-alpha in the conditioned media is inhibited by taurine chloramine

Immunopharmacology, 1996

Taurine chloramine (Tau-Cl) inhibits production of nitric oxide (NO) by activated peritoneal macr... more Taurine chloramine (Tau-Cl) inhibits production of nitric oxide (NO) by activated peritoneal macrophages and attenuates accumulation of tumor necrosis factor-alpha (TNF-alpha) in the culture media, similar to that previously reported for activated RAW 264.7 cells. In addition, the effect of Tau-Cl and taurine on superoxide anion (O2-) production in murine peritoneal exudate polymorphonuclear leukocytes (PMN) was examined. Tau-Cl inhibited O2- production in a manner that was dose-dependent and reversible. Taurine also inhibited O2- production by stimulated PMN, but at higher concentrations and to a lesser extent than Tau-Cl. The effects of taurine on O2- production was attributed to the in vitro formation of Tau-Cl catalyzed by PMN associated halide-dependent myeloperoxidase. In contrast, production of NO by activated peritoneal macrophages and accumulation of TNF-alpha in the media was inhibited by Tau-Cl while taurine was without effect. These data lend support to the notion that T...

Taurine Protects against Oxidant-Induced Lung Injury: Possible Mechanism(s) of Action

Advances in Experimental Medicine and Biology, 1994

It is thought that oxidant-induced tissue damage is not a direct effect of the oxidant per se, bu... more It is thought that oxidant-induced tissue damage is not a direct effect of the oxidant per se, but rather results from the inflammatory response that occurs thereafter. As a result of inflammation following oxidant exposure, there are neutrophils, monocytes, and macrophages with myeloperoxidase-H2O2-halide activity in the lung. Leukocytes and especially neutrophils contain high intracellular concentrations (22-50mM) of taurine (6, 8, 11, 20). Taurine acts as a trap for toxic hypochlorous acid (HOCl) and forms the less reactive metabolite, N-chlorotaurine (5-6). Thus, the biological activity of halide-dependent myeloperoxidase may be regulated by endogenous taurine. Although taurine had no effect in the present study, polymorphonuclear leukocytes have an active myeloperoxidase system capable of producing N-chlorotaurine (9, 19) and would be present at the site of inflammation in oxidant-exposed lungs. Our data suggest that taurine via N-chlorotaurine formation may protect the lung from oxidant injury, at least in part, by inhibiting production of nitrite and TNF-alpha. Moreover, lavage cells isolated from rats pretreated with taurine and exposed to O3 have a significant decrease in the production of nitrite and TNF-alpha, compared with lavage cells from rats exposed to O3 without taurine supplementation (preliminary studies). Both the concentration of taurine and the effects of N-chlorotaurine strengthen the potential impact of this chlorinated amine in vivo. N-Chlorotaurine may protect against oxidant-induced lung injury by inhibiting production of nitrite and the release of TNF-alpha which are both known to be directly linked to tissue injury.

Journal of amino acids, 2014

We engineered a CSAD KO mouse to investigate the physiological roles of taurine. The disruption o... more We engineered a CSAD KO mouse to investigate the physiological roles of taurine. The disruption of the CSAD gene was verified by Southern, Northern, and Western blotting. HPLC indicated an 83% decrease of taurine concentration in the plasma of CSAD(-/-). Although CSAD(-/-) generation (G)1 and G2 survived, offspring from G2 CSAD(-/-) had low brain and liver taurine concentrations and most died within 24 hrs of birth. Taurine concentrations in G3 CSAD(-/-) born from G2 CSAD(-/-) treated with taurine in the drinking water were restored and survival rates of G3 CSAD(-/-) increased from 15% to 92%. The mRNA expression of CDO, ADO, and TauT was not different in CSAD(-/-) compared to WT and CSAD mRNA was not expressed in CSAD(-/-). Expression of Gpx 1 and 3 was increased significantly in CSAD(-/-) and restored to normal levels with taurine supplementation. Lactoferrin and the prolactin receptor were significantly decreased in CSAD(-/-). The prolactin receptor was restored with taurine supp...

Inflammatory mediators are inhibited by a taurine metabolite in CpG oligodeoxynucleotide and IFN-r activated macrophage cell line

Journal of drugs in dermatology : JDD, 2013

Taurine plays an important role in brain and retinal development, and has an antiinflammatory and... more Taurine plays an important role in brain and retinal development, and has an antiinflammatory and antioxidant function. Taurine chloramine (Tau-Cl) is produced in polymorphonuclear leukocytes via the myeloperoxidase/halide system. We previously demonstrated that Tau-Cl inhibits the production of nitric oxide (NO) and TNF-α in human and murine macrophages activated with IFN-γ in combination with individual Toll-like receptor (TLR) ligands including those for TLR2 and/or TLR4. In the current study, we further explored the effects of Tau-Cl in RAW 264.7 cells stimulated with the TLR9 ligand CpG oligodeoxynucleotide (ODN). Specifically, we examined the effect of CpG ODN plus IFN-γ on the production of NO and TNF-α, and the effect of Tau-Cl on this process. Our findings show that CpG ODN plus IFN-γ-activated RAW 264.7 cells secrete high levels of NO and TNF-α, and that Tau-Cl (0.8 mM) inhibits this effect in a dose-dependent manner, more potently inhibiting the production of NO (99% inhi...

Taurine chloramine inhibits NO and TNF-α production in zymosan plus interferon-γ activated RAW 264.7 cells

Journal of drugs in dermatology : JDD, 2011

Taurine is present abundantly in various tissues, especially in leukocytes embattled to foreign i... more Taurine is present abundantly in various tissues, especially in leukocytes embattled to foreign invaders such as microorganisms or oxidants. Taurine-chloramine (Tau-Cl) is produced from taurine at the site of inflammation via the myeloperoxidase-halide pathway in leukocytes induced by oxidants and/or infectious materials. Previously, our data demonstrated that Tau-Cl inhibited nitric oxide (NO) production and TNF-α secretion induced by lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR-4) ligand or lipoarabinomannan (LAM), a TLR-2 ligand plus interferon-γ (IFN-γ) in peritoneal macrophages or RAW 264.7 cells. Zymosan, a β-glucan of yeast cell wall, is a ligand for TLR-2 and dectin-1 and stimulates macrophages to produce proinflammatory mediators such as NO and TNF-α. Based on our previous data, we examined the effect of zymosan and IFN-γ induced production of NO and TNF-α in the absence or presence of Tau-Cl or taurine using RAW 264.7 cells. Production of NO and secretion of TNF-α...

Taurine reduces lung inflammation and fibrosis caused by bleomycin

Advances in experimental medicine and biology, 2003

Altered Lymphocyte Proliferation and Innate Immune Function in Scrapie 139A- and ME7-Infected Mice

Viral Immunology, 2013

Lymphoid organs play an important role in prion disease development and progression. While the ro... more Lymphoid organs play an important role in prion disease development and progression. While the role of lymphoid organs and changes in immune-related genes have been extensively investigated in scrapie-infected animals, innate immunity has not. Previous studies examined lymphocyte function in scrapie-infected C3H/HeJ mice, which exhibit defects in lipopolysaccharide (LPS) response now known to result from a mutation in Toll-like receptor (TLR) 4. We examined immune function in scrapie-infected CD1 mice, which are LPS responders. Lymphocyte proliferation from CD1 mice infected with either 139A or ME7 scrapie was measured in response to concanavalin (Con) A or LPS at 1 and 3 months after infection. Following LPS exposure, mice infected 3 months with ME7, but not 139A, demonstrated significantly decreased lymphocyte proliferation compared to controls. After Con A exposure, lymphocyte proliferation in scrapie-infected mice did not differ from controls. Gender-specific comparison of lymphocyte proliferation showed significant decreases in mitogenic responses in females infected 3 months with either 139A or ME7, compared to controls. Males infected for 3 months with ME7, but not 139A, showed significantly decreased proliferation after lymphocyte exposure to LPS, but not Con A. Neither gender showed changes in lymphocyte proliferation after 1 month of scrapie infection. Innate immune activation of peritoneal macrophages was determined via production of nitric oxide (NO), IL-6, and TNF-α after exposure to TLR ligands. TNF-α and IL-6 production were reduced in macrophages from females infected with either scrapie strain for 3 months, while NO production after TLR agonist plus IFN-γ exposure was decreased in both females and males infected for 3 months with 139A, compared to ME7. These data demonstrated altered innate immunity, suggesting hormonal and/or other gender-specific regulation may contribute to gender differences in some immune functions. Our data demonstrate lymphocyte proliferation and innate immune functioning in scrapie-infected mice deteriorate with disease progression.

Regulation of nitric oxide induced by mycobacterial lipoarabinomannan in murine macrophages: Effects of interferon-β and taurine-chloramine

International Journal of Leprosy and Other Mycobacterial Diseases, 2000

Inflammatory mediators are inhibited by a taurine metabolite in CpG oligodeoxynucleotide and IFN-r activated macrophage cell line

Journal of Drugs in Dermatology Jdd, May 1, 2013

Taurine plays an important role in brain and retinal development, and has an antiinflammatory and... more Taurine plays an important role in brain and retinal development, and has an antiinflammatory and antioxidant function. Taurine chloramine (Tau-Cl) is produced in polymorphonuclear leukocytes via the myeloperoxidase/halide system. We previously demonstrated that Tau-Cl inhibits the production of nitric oxide (NO) and TNF-α in human and murine macrophages activated with IFN-γ in combination with individual Toll-like receptor (TLR) ligands including those for TLR2 and/or TLR4. In the current study, we further explored the effects of Tau-Cl in RAW 264.7 cells stimulated with the TLR9 ligand CpG oligodeoxynucleotide (ODN). Specifically, we examined the effect of CpG ODN plus IFN-γ on the production of NO and TNF-α, and the effect of Tau-Cl on this process. Our findings show that CpG ODN plus IFN-γ-activated RAW 264.7 cells secrete high levels of NO and TNF-α, and that Tau-Cl (0.8 mM) inhibits this effect in a dose-dependent manner, more potently inhibiting the production of NO (99% inhibition) than that of TNF-α (48% inhibition). Nitric oxide synthase (iNOS) protein was also induced by CpG ODN plus IFN-γ, and was also inhibited by Tau-Cl. Furthermore, while CpG ODN plus IFN-γ induced TNF-α and iNOS mRNAs, Tau-Cl transiently suppressed this effect. Taurine itself had no effects on any of these processes. Our findings in a macrophage cell line demonstrate that Tau-Cl inhibits proinflammatory mediators resulting from TLR9 activation, and have implications for the utility of Tau-Cl in scenarios where such activation is deleterious such as in autoimmune conditions or infections in which overwhelming inflammation may occur. CpG ODNs and Tau-Cl both have potential for topical treatment of autoimmune conditions, including psoriasis, vitiligo, and alopecia areata. As CpG ODNs may, under some conditions, up-regulate Tregs, addition of Tau-Cl to CpG ODN topical formulations has potential for improving cancer immunotherapy.

Deficient Tumor Necrosis Factor-α Production in Lipoarabinomannan Activated Macrophages from Toll-like Receptor-4 Deficient Mice: Implication for Mycobacterial Susceptibility

International Journal of Leprosy and Other Mycobacterial Diseases, 2003

Taurine Protects Rat Bronchioles from Acute Ozone-Induced Lung Inflammation and Hyperplasia

Experimental Lung Research, 1995

Ozone is a potent respiratory irritant known to induce lung injury in humans and experimental ani... more Ozone is a potent respiratory irritant known to induce lung injury in humans and experimental animals. The present studies determined if ozone-induced lung inflammation was modified by pretreatment of animals with taurine, a detoxifying antioxidant. Rats were pretreated for 10 days with 5% taurine in their drinking water (controls received water only) prior to exposure to 2 ppm ozone for 3 h. At 2, 6, 12, 24, 48, and 72 h after ozone exposure, rats were anesthetized and the lungs were perfusion-fixed for histopathologic evaluation. An additional group of rats was used to examine bronchoalveolar lavage cell counts and hydroxyproline levels. A count of bronchoalveolar lavage cells 48 h after ozone exposure showed significantly fewer total inflammatory cells and fewer polymorphonuclear leukocytes accompanied by a reduction in hydroxyproline in the lavage fluid of ozone-exposed rats pretreated with taurine compared to rats that did not receive taurine. Light microscopy revealed an inflammatory cell infiltrate in the lungs of rats exposed to ozone. This was followed by focal hyperplasia in the terminal and respiratory bronchioles. Rats pretreated with taurine and then exposed to ozone showed none of these alterations. In addition, although there was a significant reduction in cell proliferation as measured by DNA precursor incorporation in the lungs of rats pretreated with taurine prior to ozone exposure compared to unsupplemented rats, the distribution of labeled cells was the same in taurine supplemented and unsupplemented groups. Also, significantly higher levels of taurine were found in the plasma, whole blood, and lavage fluid of rats pretreated with dietary taurine compared to rats that received water only. The results suggest that supplemental taurine protects rat lung epithelium from acute ozone-induced lung inflammation and hyperplasia.

Effect of thalidomide on nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells

Journal of Drugs in Dermatology Jdd, Apr 1, 2010

Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 ... more Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 (T helper 1) immunity measured by increased IL-2 (Interleukin-2) and gamma interferon. The authors have assessed the effect of thalidomide and analogues, di- and tri-thiothalidomide, on a lipopolysaccharide (LPS) activated macrophage cell line (RAW 246.7 cells). The authors' findings showed that nitric oxide (NO) was significantly inhibited by thalidomide (15%) and its analogues (di-thiothalidomide; 15%, tri-thiothalidomide; 32%). The proinflammatory molecules TNF-alpha (tumor necrosis factor-alpha) and IL-6 were not significantly inhibited. Pretreatment with thalidomide and analogues before activation was not different from simultaneous treatment. Inhibition of inducible nitric oxide synthase (iNOS) may prove to be an important target for the anti-inflammatory and anti-cancer effects of thalidomide and related immunomodulatory drugs (IMiDs).

Taurine protects against oxidant-induced lung injury: possible mechanism(s) of action

Advances in Experimental Medicine and Biology, Feb 1, 1994

It is thought that oxidant-induced tissue damage is not a direct effect of the oxidant per se, bu... more It is thought that oxidant-induced tissue damage is not a direct effect of the oxidant per se, but rather results from the inflammatory response that occurs thereafter. As a result of inflammation following oxidant exposure, there are neutrophils, monocytes, and macrophages with myeloperoxidase-H2O2-halide activity in the lung. Leukocytes and especially neutrophils contain high intracellular concentrations (22-50mM) of taurine (6, 8, 11, 20). Taurine acts as a trap for toxic hypochlorous acid (HOCl) and forms the less reactive metabolite, N-chlorotaurine (5-6). Thus, the biological activity of halide-dependent myeloperoxidase may be regulated by endogenous taurine. Although taurine had no effect in the present study, polymorphonuclear leukocytes have an active myeloperoxidase system capable of producing N-chlorotaurine (9, 19) and would be present at the site of inflammation in oxidant-exposed lungs. Our data suggest that taurine via N-chlorotaurine formation may protect the lung from oxidant injury, at least in part, by inhibiting production of nitrite and TNF-alpha. Moreover, lavage cells isolated from rats pretreated with taurine and exposed to O3 have a significant decrease in the production of nitrite and TNF-alpha, compared with lavage cells from rats exposed to O3 without taurine supplementation (preliminary studies). Both the concentration of taurine and the effects of N-chlorotaurine strengthen the potential impact of this chlorinated amine in vivo. N-Chlorotaurine may protect against oxidant-induced lung injury by inhibiting production of nitrite and the release of TNF-alpha which are both known to be directly linked to tissue injury.

Neurochemical Research, 2004

Taurine is a semiessential amino acid that is not incorporated into proteins. In mammalian tissue... more Taurine is a semiessential amino acid that is not incorporated into proteins. In mammalian tissues, taurine is ubiquitous and is the most abundant free amino acid in the heart, retina, skeletal muscle, and leukocytes. Taurine reaches up to 50 mM concentration in leukocytes. Taurine has been shown to be tissue-protective in many models of oxidant-induced injury. One possibility is that taurine reacts with HOCl, produced by the myeloperoxidase (MPO) pathway, to produce the more stable but less toxic taurine chloramine (Tau-Cl). However, data from several laboratories demonstrate that Tau-Cl is a powerful regulator of the immune system. Specifically, Tau-Cl has been shown to downregulate the production of proinflammatory mediators in both rodent and human leukocytes. Recent molecular studies on the function of taurine provide evidence that taurine is a constituent of biological macromolecules. Specifically, two novel taurine-containing modified uridines have been found in both human and bovine mitrochondria. In studies on mechanism of action, Tau-Cl inhibits the activation of NFB, a potent signal transducer for inflammatory cytokines, by oxidation of IB␣ at methionine 45 . Taurine transporter knockout mice show reduced taurine, reduced fertility, and loss of vision resulting from severe retinal degeneration, which was found to be due to apoptosis. Apoptosis induced by amino chloramines is a current and important finding because oxidants derived from leukocytes play a key role in killing pathogens. The fundamental importance of taurine in adaptive and acquired immunity will be revealed using genetic manipulation.

International Immunopharmacology, May 1, 2009

Taurine has been shown to protect against lung injury induced by various oxidants including ozone... more Taurine has been shown to protect against lung injury induced by various oxidants including ozone, nitrogen dioxide, amiodarone, and paraquat and to protect against bleomycin-induced lung injury in combination with niacin. In this study, Spraque-Dawley rats were treated with 5% taurine in the drinking water for 10 days prior to bleomycin instillation. Fibrosis in the rats pretreated with taurine (BT) was absent, along with fewer inflammatory infiltrates compared to the untreated rats (BW). A significant decrease in the number of PMNs and a decrease in hydroxyproline levels were found in the bronchoalveolar lavage fluid in the BT group compared to the BW group. By immunohistochemical staining, inducible nitric oxide synthase was evident in the lungs of bleomycintreated rats, and minimal when rats were treated with taurine. Tumor necrosis factor-alpha (TNF-α) as measured by immunohistochemical staining, was present in lungs of both taurine-treated and untreated rats, but was more abundant in the BW group compared to the BT group. In addition, decreased ICAM presentation was detected by EM immunogold staining in the BT group compared to the BW group. These data demonstrate that rats pretreated with 5% taurine in their drinking water prior to bleomycin instillation are protected from fibrosis, inflammatory infiltrates, as well as nitric oxide and TNF-α production, which are hallmarks of bleomycin lung injury.

Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo

Amino acids, Jan 20, 2015

The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mou... more The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mouse are not able to synthesize hypotaurine/taurine by the cysteine/cysteine sulfinate pathway and have very low tissue taurine levels. These mice provide excellent models for studying the effects of taurine on biological processes. Using these mouse models, we identified betaine:homocysteine methyltransferase (BHMT) as a protein whose in vivo expression is robustly regulated by taurine. BHMT levels are low in liver of both Cdo1-null and Csad-null mice, but are restored to wild-type levels by dietary taurine supplementation. A lack of BHMT activity was indicated by an increase in the hepatic betaine level. In contrast to observations in liver of Cdo1-null and Csad-null mice, BHMT was not affected by taurine supplementation of primary hepatocytes from these mice. Likewise, CSAD abundance was not affected by taurine supplementation of primary hepatocytes, although it was robustly upregulated...

Taurine chloramine inhibits the production of superoxide anion, IL-6 and IL-8 in activated human polymorphonuclear leukocytes

Advances in experimental medicine and biology, 1998

Search by Subject Search using Medical Subject Headings (< b> MeSH</b&gt... more Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.

A novel cysteine sulfinic Acid decarboxylase knock-out mouse: comparison between newborn and weanling mice

Advances in experimental medicine and biology, 2015

Effect of thalidomide on nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells

Journal of drugs in dermatology : JDD, 2010

Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 ... more Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 (T helper 1) immunity measured by increased IL-2 (Interleukin-2) and gamma interferon. The authors have assessed the effect of thalidomide and analogues, di- and tri-thiothalidomide, on a lipopolysaccharide (LPS) activated macrophage cell line (RAW 246.7 cells). The authors' findings showed that nitric oxide (NO) was significantly inhibited by thalidomide (15%) and its analogues (di-thiothalidomide; 15%, tri-thiothalidomide; 32%). The proinflammatory molecules TNF-alpha (tumor necrosis factor-alpha) and IL-6 were not significantly inhibited. Pretreatment with thalidomide and analogues before activation was not different from simultaneous treatment. Inhibition of inducible nitric oxide synthase (iNOS) may prove to be an important target for the anti-inflammatory and anti-cancer effects of thalidomide and related immunomodulatory drugs (IMiDs).

Taurine chloramine attenuates the hydrolytic activity of matrix metalloproteinase-9 in LPS-activated murine peritoneal macrophages

Advances in experimental medicine and biology, 2000

The production of superoxide anion and nitric oxide by cultured murine leukocytes and the accumulation of TNF-alpha in the conditioned media is inhibited by taurine chloramine

Immunopharmacology, 1996

Taurine chloramine (Tau-Cl) inhibits production of nitric oxide (NO) by activated peritoneal macr... more Taurine chloramine (Tau-Cl) inhibits production of nitric oxide (NO) by activated peritoneal macrophages and attenuates accumulation of tumor necrosis factor-alpha (TNF-alpha) in the culture media, similar to that previously reported for activated RAW 264.7 cells. In addition, the effect of Tau-Cl and taurine on superoxide anion (O2-) production in murine peritoneal exudate polymorphonuclear leukocytes (PMN) was examined. Tau-Cl inhibited O2- production in a manner that was dose-dependent and reversible. Taurine also inhibited O2- production by stimulated PMN, but at higher concentrations and to a lesser extent than Tau-Cl. The effects of taurine on O2- production was attributed to the in vitro formation of Tau-Cl catalyzed by PMN associated halide-dependent myeloperoxidase. In contrast, production of NO by activated peritoneal macrophages and accumulation of TNF-alpha in the media was inhibited by Tau-Cl while taurine was without effect. These data lend support to the notion that T...

Taurine Protects against Oxidant-Induced Lung Injury: Possible Mechanism(s) of Action

Advances in Experimental Medicine and Biology, 1994

It is thought that oxidant-induced tissue damage is not a direct effect of the oxidant per se, bu... more It is thought that oxidant-induced tissue damage is not a direct effect of the oxidant per se, but rather results from the inflammatory response that occurs thereafter. As a result of inflammation following oxidant exposure, there are neutrophils, monocytes, and macrophages with myeloperoxidase-H2O2-halide activity in the lung. Leukocytes and especially neutrophils contain high intracellular concentrations (22-50mM) of taurine (6, 8, 11, 20). Taurine acts as a trap for toxic hypochlorous acid (HOCl) and forms the less reactive metabolite, N-chlorotaurine (5-6). Thus, the biological activity of halide-dependent myeloperoxidase may be regulated by endogenous taurine. Although taurine had no effect in the present study, polymorphonuclear leukocytes have an active myeloperoxidase system capable of producing N-chlorotaurine (9, 19) and would be present at the site of inflammation in oxidant-exposed lungs. Our data suggest that taurine via N-chlorotaurine formation may protect the lung from oxidant injury, at least in part, by inhibiting production of nitrite and TNF-alpha. Moreover, lavage cells isolated from rats pretreated with taurine and exposed to O3 have a significant decrease in the production of nitrite and TNF-alpha, compared with lavage cells from rats exposed to O3 without taurine supplementation (preliminary studies). Both the concentration of taurine and the effects of N-chlorotaurine strengthen the potential impact of this chlorinated amine in vivo. N-Chlorotaurine may protect against oxidant-induced lung injury by inhibiting production of nitrite and the release of TNF-alpha which are both known to be directly linked to tissue injury.

Journal of amino acids, 2014

We engineered a CSAD KO mouse to investigate the physiological roles of taurine. The disruption o... more We engineered a CSAD KO mouse to investigate the physiological roles of taurine. The disruption of the CSAD gene was verified by Southern, Northern, and Western blotting. HPLC indicated an 83% decrease of taurine concentration in the plasma of CSAD(-/-). Although CSAD(-/-) generation (G)1 and G2 survived, offspring from G2 CSAD(-/-) had low brain and liver taurine concentrations and most died within 24 hrs of birth. Taurine concentrations in G3 CSAD(-/-) born from G2 CSAD(-/-) treated with taurine in the drinking water were restored and survival rates of G3 CSAD(-/-) increased from 15% to 92%. The mRNA expression of CDO, ADO, and TauT was not different in CSAD(-/-) compared to WT and CSAD mRNA was not expressed in CSAD(-/-). Expression of Gpx 1 and 3 was increased significantly in CSAD(-/-) and restored to normal levels with taurine supplementation. Lactoferrin and the prolactin receptor were significantly decreased in CSAD(-/-). The prolactin receptor was restored with taurine supp...

Inflammatory mediators are inhibited by a taurine metabolite in CpG oligodeoxynucleotide and IFN-r activated macrophage cell line

Journal of drugs in dermatology : JDD, 2013

Taurine plays an important role in brain and retinal development, and has an antiinflammatory and... more Taurine plays an important role in brain and retinal development, and has an antiinflammatory and antioxidant function. Taurine chloramine (Tau-Cl) is produced in polymorphonuclear leukocytes via the myeloperoxidase/halide system. We previously demonstrated that Tau-Cl inhibits the production of nitric oxide (NO) and TNF-α in human and murine macrophages activated with IFN-γ in combination with individual Toll-like receptor (TLR) ligands including those for TLR2 and/or TLR4. In the current study, we further explored the effects of Tau-Cl in RAW 264.7 cells stimulated with the TLR9 ligand CpG oligodeoxynucleotide (ODN). Specifically, we examined the effect of CpG ODN plus IFN-γ on the production of NO and TNF-α, and the effect of Tau-Cl on this process. Our findings show that CpG ODN plus IFN-γ-activated RAW 264.7 cells secrete high levels of NO and TNF-α, and that Tau-Cl (0.8 mM) inhibits this effect in a dose-dependent manner, more potently inhibiting the production of NO (99% inhi...

Taurine chloramine inhibits NO and TNF-α production in zymosan plus interferon-γ activated RAW 264.7 cells

Journal of drugs in dermatology : JDD, 2011

Taurine is present abundantly in various tissues, especially in leukocytes embattled to foreign i... more Taurine is present abundantly in various tissues, especially in leukocytes embattled to foreign invaders such as microorganisms or oxidants. Taurine-chloramine (Tau-Cl) is produced from taurine at the site of inflammation via the myeloperoxidase-halide pathway in leukocytes induced by oxidants and/or infectious materials. Previously, our data demonstrated that Tau-Cl inhibited nitric oxide (NO) production and TNF-α secretion induced by lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR-4) ligand or lipoarabinomannan (LAM), a TLR-2 ligand plus interferon-γ (IFN-γ) in peritoneal macrophages or RAW 264.7 cells. Zymosan, a β-glucan of yeast cell wall, is a ligand for TLR-2 and dectin-1 and stimulates macrophages to produce proinflammatory mediators such as NO and TNF-α. Based on our previous data, we examined the effect of zymosan and IFN-γ induced production of NO and TNF-α in the absence or presence of Tau-Cl or taurine using RAW 264.7 cells. Production of NO and secretion of TNF-α...

Taurine reduces lung inflammation and fibrosis caused by bleomycin

Advances in experimental medicine and biology, 2003

Altered Lymphocyte Proliferation and Innate Immune Function in Scrapie 139A- and ME7-Infected Mice

Viral Immunology, 2013

Lymphoid organs play an important role in prion disease development and progression. While the ro... more Lymphoid organs play an important role in prion disease development and progression. While the role of lymphoid organs and changes in immune-related genes have been extensively investigated in scrapie-infected animals, innate immunity has not. Previous studies examined lymphocyte function in scrapie-infected C3H/HeJ mice, which exhibit defects in lipopolysaccharide (LPS) response now known to result from a mutation in Toll-like receptor (TLR) 4. We examined immune function in scrapie-infected CD1 mice, which are LPS responders. Lymphocyte proliferation from CD1 mice infected with either 139A or ME7 scrapie was measured in response to concanavalin (Con) A or LPS at 1 and 3 months after infection. Following LPS exposure, mice infected 3 months with ME7, but not 139A, demonstrated significantly decreased lymphocyte proliferation compared to controls. After Con A exposure, lymphocyte proliferation in scrapie-infected mice did not differ from controls. Gender-specific comparison of lymphocyte proliferation showed significant decreases in mitogenic responses in females infected 3 months with either 139A or ME7, compared to controls. Males infected for 3 months with ME7, but not 139A, showed significantly decreased proliferation after lymphocyte exposure to LPS, but not Con A. Neither gender showed changes in lymphocyte proliferation after 1 month of scrapie infection. Innate immune activation of peritoneal macrophages was determined via production of nitric oxide (NO), IL-6, and TNF-α after exposure to TLR ligands. TNF-α and IL-6 production were reduced in macrophages from females infected with either scrapie strain for 3 months, while NO production after TLR agonist plus IFN-γ exposure was decreased in both females and males infected for 3 months with 139A, compared to ME7. These data demonstrated altered innate immunity, suggesting hormonal and/or other gender-specific regulation may contribute to gender differences in some immune functions. Our data demonstrate lymphocyte proliferation and innate immune functioning in scrapie-infected mice deteriorate with disease progression.