Nicos A Petasis | University of Southern California (original) (raw)
Dr. Nicos A. Petasis is the holder of the Harold E.
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Papers by Nicos A Petasis
Multicomponent Reactions, 2005
The Faseb Journal, Apr 1, 2009
American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012
Apoptosis is essential for removal of neutrophils from inflamed tissues and efficient resolution ... more Apoptosis is essential for removal of neutrophils from inflamed tissues and efficient resolution of inflammation. Myeloperoxidase (MPO), abundantly expressed in neutrophils, not only generates cytotoxic oxidants but also signals through the beta(2) integrin Mac-1 to rescue neutrophils from constitutive apoptosis, thereby prolonging inflammation. Because aspirin-triggered 15-epi-lipoxin A(4) (15-epi-LXA(4)) modulates Mac-1 expression, we investigated the impact of 15-epi-LXA(4) on MPO suppression of neutrophil apoptosis and MPO-mediated neutrophil-dependent acute lung injury. Human neutrophils were cultured with MPO with or without 15-epi-LXA(4) to investigate development of apoptosis. Acute lung injury was produced by intratracheal injection of carrageenan plus MPO or intraperitoneal injection of live Escherichia coli in mice, and the animals were treated with 15-epi-LXA(4) at the peak of inflammation. 15-Epi-LXA(4) through down-regulation of Mac-1 expression promoted apoptosis of human neutrophils by attenuating MPO-induced activation of extracellular signal-regulated kinase and Akt-mediated phosphorylation of Bad and by reducing expression of the antiapoptotic protein Mcl-1, thereby aggravating mitochondrial dysfunction. The proapoptotic effect of 15-epi-LXA(4) was dominant over MPO-mediated effects even when it was added at 4 hours post MPO. In mice, treatment with 15-epi-LXA(4) accelerated the resolution of established carrageenan plus MPO-evoked as well as E. coli-induced neutrophil-dependent pulmonary inflammation through redirecting neutrophils to caspase-mediated cell death and facilitating their removal by macrophages. These results demonstrate that aspirin-triggered 15-epi-LXA(4) enhances resolution of inflammation by overriding the powerful antiapoptosis signal from MPO, thereby demonstrating a hitherto unrecognized mechanism by which aspirin promotes resolution of inflammation.
The Journal of Pharmacology and Experimental Therapeutics, Nov 1, 1998
Journal of the American Chemical Society, 1990
Cheminform, 2010
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
J Am Chem Soc, 1998
... Ilia A. Zavialov. Department of Chemistry Loker Hydrocarbon Research Institute University of ... more ... Ilia A. Zavialov. Department of Chemistry Loker Hydrocarbon Research Institute University of Southern California Los Angeles, California 90089-1661. J. Am. Chem. Soc. ... 3 It is also a common subunit of a large variety of bioactive compounds, such as many protease inhibitors. ...
Scientific reports, 2016
Resolvins of the D-series are specialized pro-resolving lipid mediators that regulate cellular re... more Resolvins of the D-series are specialized pro-resolving lipid mediators that regulate cellular response by orchestrating resolution networks involved in host responses to injury and infection. Here, endogenous resolvin D4 was identified in human tissues and found to persist late into the resolution phase of acute murine Staphylococcus aureus infections. Completion of the first total synthesis of resolvin D4 established the absolute stereochemical configuration of RvD4 confirmed by matching with endogenous RvD4 from resolving exudates in dorsal pouch S. aureus infections. In vivo, RvD4 (ng/mouse) reduced neutrophilic infiltration (~40%) and enhanced uptake of apoptotic PMN (51%) by human dermal fibroblasts at concentrations as low as 0.1 nM. These results establish the complete stereochemistry of RvD4 as 4S,5R,17S-trihydroxydocosa-6E,8E,10Z,13Z,15E,19Z-hexaenoic acid and its novel pro-resolving actions in S. aureus infections as well as its potent ability to stimulate clearance of ap...
J Am Chem Soc, 1992
... Although compounds 16 may be formed directly from the cumulenolate 15, they can also be deriv... more ... Although compounds 16 may be formed directly from the cumulenolate 15, they can also be derived via the alkyne to allene isomerization of aldol product 18 obtained from the alkynenolate 17. ... Chem. Soc. 1992, 114. 794. (41) (a) Williard, PG; Nichols, M. A. J. Am. Chem. SOC. ...
Multicomponent Reactions, 2005
The Faseb Journal, Apr 1, 2009
American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012
Apoptosis is essential for removal of neutrophils from inflamed tissues and efficient resolution ... more Apoptosis is essential for removal of neutrophils from inflamed tissues and efficient resolution of inflammation. Myeloperoxidase (MPO), abundantly expressed in neutrophils, not only generates cytotoxic oxidants but also signals through the beta(2) integrin Mac-1 to rescue neutrophils from constitutive apoptosis, thereby prolonging inflammation. Because aspirin-triggered 15-epi-lipoxin A(4) (15-epi-LXA(4)) modulates Mac-1 expression, we investigated the impact of 15-epi-LXA(4) on MPO suppression of neutrophil apoptosis and MPO-mediated neutrophil-dependent acute lung injury. Human neutrophils were cultured with MPO with or without 15-epi-LXA(4) to investigate development of apoptosis. Acute lung injury was produced by intratracheal injection of carrageenan plus MPO or intraperitoneal injection of live Escherichia coli in mice, and the animals were treated with 15-epi-LXA(4) at the peak of inflammation. 15-Epi-LXA(4) through down-regulation of Mac-1 expression promoted apoptosis of human neutrophils by attenuating MPO-induced activation of extracellular signal-regulated kinase and Akt-mediated phosphorylation of Bad and by reducing expression of the antiapoptotic protein Mcl-1, thereby aggravating mitochondrial dysfunction. The proapoptotic effect of 15-epi-LXA(4) was dominant over MPO-mediated effects even when it was added at 4 hours post MPO. In mice, treatment with 15-epi-LXA(4) accelerated the resolution of established carrageenan plus MPO-evoked as well as E. coli-induced neutrophil-dependent pulmonary inflammation through redirecting neutrophils to caspase-mediated cell death and facilitating their removal by macrophages. These results demonstrate that aspirin-triggered 15-epi-LXA(4) enhances resolution of inflammation by overriding the powerful antiapoptosis signal from MPO, thereby demonstrating a hitherto unrecognized mechanism by which aspirin promotes resolution of inflammation.
The Journal of Pharmacology and Experimental Therapeutics, Nov 1, 1998
Journal of the American Chemical Society, 1990
Cheminform, 2010
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
J Am Chem Soc, 1998
... Ilia A. Zavialov. Department of Chemistry Loker Hydrocarbon Research Institute University of ... more ... Ilia A. Zavialov. Department of Chemistry Loker Hydrocarbon Research Institute University of Southern California Los Angeles, California 90089-1661. J. Am. Chem. Soc. ... 3 It is also a common subunit of a large variety of bioactive compounds, such as many protease inhibitors. ...
Scientific reports, 2016
Resolvins of the D-series are specialized pro-resolving lipid mediators that regulate cellular re... more Resolvins of the D-series are specialized pro-resolving lipid mediators that regulate cellular response by orchestrating resolution networks involved in host responses to injury and infection. Here, endogenous resolvin D4 was identified in human tissues and found to persist late into the resolution phase of acute murine Staphylococcus aureus infections. Completion of the first total synthesis of resolvin D4 established the absolute stereochemical configuration of RvD4 confirmed by matching with endogenous RvD4 from resolving exudates in dorsal pouch S. aureus infections. In vivo, RvD4 (ng/mouse) reduced neutrophilic infiltration (~40%) and enhanced uptake of apoptotic PMN (51%) by human dermal fibroblasts at concentrations as low as 0.1 nM. These results establish the complete stereochemistry of RvD4 as 4S,5R,17S-trihydroxydocosa-6E,8E,10Z,13Z,15E,19Z-hexaenoic acid and its novel pro-resolving actions in S. aureus infections as well as its potent ability to stimulate clearance of ap...
J Am Chem Soc, 1992
... Although compounds 16 may be formed directly from the cumulenolate 15, they can also be deriv... more ... Although compounds 16 may be formed directly from the cumulenolate 15, they can also be derived via the alkyne to allene isomerization of aldol product 18 obtained from the alkynenolate 17. ... Chem. Soc. 1992, 114. 794. (41) (a) Williard, PG; Nichols, M. A. J. Am. Chem. SOC. ...