Increased mortality and inflammation in tumor necrosis factor-stimulated gene-14 transgenic mice after ischemia and reperfusion injury - PubMed (original) (raw)
Increased mortality and inflammation in tumor necrosis factor-stimulated gene-14 transgenic mice after ischemia and reperfusion injury
Danielle G Souza et al. Am J Pathol. 2002 May.
Erratum in
- Am J Pathol 2003 Jan;162(1):359. Martins Mauro T [corrected to Teixeira Mauro M]
Abstract
TSG-14/PTX3 is a gene inducible by tumor necrosis factor (TNF)-alpha, interleukin-1 beta, and lipopolysaccharide in fibroblasts, macrophages, and endothelial cells. It encodes a 42-kd secreted glycoprotein that belongs to the pentraxin family of acute-phase proteins. Recently, we demonstrated that TSG-14 transgenic mice (TSG-14tg) overexpressing the murine TSG-14 gene under control of its own promoter are more resistant to lipopolysaccharide-induced shock and to polymicrobial sepsis caused by cecal ligation and puncture. Here we show that after ischemia and reperfusion (I/R) injury, TSG-14tg mice have an impaired survival rate, which appeared secondary to a markedly increased inflammatory response, as assessed by the local (duodenum and ileum) and remote (lung) enhancement in vascular permeability, hemorrhage, and neutrophil accumulation. Moreover, tissue concentrations of TNF-alpha, interleukin-1 beta, KC, and MCP-1 were higher in TSG-14tg as compared to wild-type mice after I/R injury. Of note, elevated TNF-alpha concentrations in serum were only observed in TSG-14tg mice and blockage of TNF-alpha action prevented lethality of TSG-14tg mice. These results demonstrate that transgenic expression of TSG-14 induces an enhanced local and systemic injury and TNF-alpha-dependent lethality after I/R. Taken together, our data point to a critical role of TSG-14 in controlling acute inflammatory response in part via the modulation of TNF-alpha expression.
Figures
Figure 1.
Kinetics of tissue injury after I/R of the SMA. CD1 WT mice were submitted to ischemia (60 minutes) of the SMA. Reperfusion was allowed for 15, 30, and 60 minutes and tissue injury (duodenum) was determined. A: Changes in vascular permeability were evaluated by measuring the extravasation of Evans blue (μg/100 mg of tissue). B: Neutrophil infiltration was determined by measurement of tissue myeloperoxidase activity, as described in Material and Methods. C: Hemorrhage was evaluated by measuring the concentration of hemoglobin in 100 mg of tissue. Data represent the average value for five mice at each time point and SEM is indicated. #, P < 0.05 and P < 0.001 for comparison of values observed after 30 minutes and 60 minutes, respectively, with the respective sham-operated group.
Figure 2.
Induced expression of the TSG-14 gene on I/R of the SMA. CD1 WT or TSG-14tg mice were sham-operated or submitted to I/R of the SMA (ischemia for 60 minutes and reperfusion for 30 minutes). Total RNA (1 μg) was isolated from the duodenum, reverse-transcribed, and used as a template for PCR as indicated in Material and Methods. PCR products were fractionated through a 1% agarose gel and detected by Southern blot using a 32Pα-dCTP-labeled TSG-14 cDNA probe. Using the same methodology, HGPRT mRNA was measured to control for RNA loading.
Figure 3.
Survival curve of CD1 and TSG-14tg mice submitted to ischemia of the SMA. Mice (n = 10 in each group) were anesthetized and submitted to ischemia of the superior mesenteric for 60 minutes. Tissue perfusion was then re-established and survival was monitored. The differences observed between WT and the two transgenic lines submitted to I/R are statistically significant, as determined by Fischer’s exact test (P < 0.05).
Figure 4.
Evaluation of tissue injury in WT and in TSG-14tg mice submitted to I/R of the SMA. WT or TSG-14tg mice having two (Tg2) or four (Tg4) copies of the transgene were sham-operated or submitted to 60 minutes of ischemia of the SMA and reperfusion was allowed for 30 minutes. A and B: Changes in vascular permeability were evaluated by measuring the extravasation of Evans blue (μg/100 mg of tissue). C and D: Neutrophil infiltration was determined by measurement of tissue myeloperoxidase activity, as described in Material and Methods. E: Hemorrhage was evaluated by measuring the concentration of hemoglobin in 100 mg of tissue. Tested organs were the duodenum (A, C, and E) and lungs (B and D). Data represent the average value for five to six mice at each time point and SEM is indicated. #, P < 0.01 for comparison with individual groups with their respective sham-operated group. *, P < 0.01 for comparisons between WT and transgenic mice submitted to I/R.
Figure 5.
Tissue damage in lungs and duodenum of WT or TSG-14tg mice submitted to I/R of the SMA. WT or TSG-14tg mice having two copies of the transgene (Tg2) were sham-operated (A and E and C and G, respectively) or submitted to 60 minutes of ischemia of the SMA and reperfusion was allowed for 30 minutes (B and D and F and H, respectively). Mice were anesthetized, sacrificed, and the duodenum (A–D) and lungs (E–H) were processed for histological analysis after H&E staining. Original magnification, ×100.
Figure 6.
Levels of TNF protein in serum and tissue of mice submitted to I/R of the SMA. WT or TSG-14tg mice having two (Tg2) or four (Tg4) copies of the transgene were sham-operated or submitted to 60 minutes of ischemia of the SMA and reperfusion was allowed for 30 minutes. Mice were anesthetized, sacrificed, and the concentration of TNF-α in serum (A), duodenum (B), ileum (C), and lungs (D) were measured by enzyme-linked immunosorbent assay. Data represent the average value for six mice at each time point and SEM is indicated. #, P < 0.01 for comparison with individual groups with their respective sham-operated group. *, P < 0.01 for comparisons between WT and transgenic mice submitted to I/R.
Figure 7.
Survival curve of mice submitted to I/R of the SMA. Mice were anesthetized and submitted to ischemia of the SMA for 60 minutes. Reperfusion was then re-established and survival was monitored. A: Comparison of survival of WT and p55−/− mice (n = 10 in each group, both groups in 129Sv/C57/BL6 background). B: Tg2 mice (CD1 background) were left untreated or injected with 3 μg of soluble TNFR1 receptor immediately before reperfusion (n = 8 in each group). Survival was monitored as indicated and survivors were sacrificed after 120 minutes. Differences between groups in A and B were compared using Fisher’s exact test and considered significant (P < 0.05).
Similar articles
- TSG-14 transgenic mice have improved survival to endotoxemia and to CLP-induced sepsis.
Dias AA, Goodman AR, Dos Santos JL, Gomes RN, Altmeyer A, Bozza PT, Horta MF, Vilcek J, Reis LF. Dias AA, et al. J Leukoc Biol. 2001 Jun;69(6):928-36. J Leukoc Biol. 2001. PMID: 11404378 - Differential regulation of TSG-14 expression in murine fibroblasts and peritoneal macrophages.
Goodman AR, Levy DE, Reis LF, Vilcek J. Goodman AR, et al. J Leukoc Biol. 2000 Mar;67(3):387-95. doi: 10.1002/jlb.67.3.387. J Leukoc Biol. 2000. PMID: 10733100 - Soluble tumor necrosis factor receptors reduce bowel ischemia-induced lung permeability and neutrophil sequestration.
Sorkine P, Setton A, Halpern P, Miller A, Rudick V, Marmor S, Klausner JM, Goldman G. Sorkine P, et al. Crit Care Med. 1995 Aug;23(8):1377-81. doi: 10.1097/00003246-199508000-00011. Crit Care Med. 1995. PMID: 7634808 - Cytokine-induced gene expression at the crossroads of innate immunity, inflammation and fertility: TSG-6 and PTX3/TSG-14.
Wisniewski HG, Vilcek J. Wisniewski HG, et al. Cytokine Growth Factor Rev. 2004 Apr-Jun;15(2-3):129-46. doi: 10.1016/j.cytogfr.2004.01.005. Cytokine Growth Factor Rev. 2004. PMID: 15110797 Review. - TSG-6: an IL-1/TNF-inducible protein with anti-inflammatory activity.
Wisniewski HG, Vilcek J. Wisniewski HG, et al. Cytokine Growth Factor Rev. 1997 Jun;8(2):143-56. doi: 10.1016/s1359-6101(97)00008-7. Cytokine Growth Factor Rev. 1997. PMID: 9244409 Review.
Cited by
- The use of occlusive dressings: influence on excisional wound healing in animal model.
Guillen MRS, Borges EL, Amorim GL, Vieira PC, Guedes ACM, Barcelos LS. Guillen MRS, et al. Acta Cir Bras. 2023 Jan 13;37(12):e371206. doi: 10.1590/acb371206. eCollection 2023. Acta Cir Bras. 2023. PMID: 36651431 Free PMC article. - Expression of pentraxin 3 in equine lungs and neutrophils.
Townsend M, Fowler B, Aulakh GK, Singh B. Townsend M, et al. Can J Vet Res. 2023 Jan;87(1):9-16. Can J Vet Res. 2023. PMID: 36606044 Free PMC article. - Blockade of the pentraxin 3/CD44 interaction attenuates lung injury-induced fibrosis.
Chi JY, Hsiao YW, Liang HY, Huang TH, Chen FW, Chen CY, Ko CY, Cheng CC, Wang JM. Chi JY, et al. Clin Transl Med. 2022 Nov;12(11):e1099. doi: 10.1002/ctm2.1099. Clin Transl Med. 2022. PMID: 36336784 Free PMC article. - Association of Tumor Necrosis Factor-α and Myeloperoxidase enzyme with Severe Asthma: A comparative study.
Aldhalmi AK, Al-Athari AJH, Makki Al-Hindy HA. Aldhalmi AK, et al. Rep Biochem Mol Biol. 2022 Jul;11(2):238-245. doi: 10.52547/rbmb.11.2.238. Rep Biochem Mol Biol. 2022. PMID: 36164624 Free PMC article. - The Combination of Phages and Faecal Microbiota Transplantation Can Effectively Treat Mouse Colitis Caused by Salmonella enterica Serovar Typhimurium.
Wang X, Xing Y, Ji Y, Xi H, Liu X, Yang L, Lei L, Han W, Gu J. Wang X, et al. Front Microbiol. 2022 Jul 7;13:944495. doi: 10.3389/fmicb.2022.944495. eCollection 2022. Front Microbiol. 2022. PMID: 35875536 Free PMC article.
References
- Aggarwal BB, Samanta A, Feldman M: TNF-alpha. Oppenheim JD Feldmann M eds. Cytokine Reference. 2001, :pp 413-434 Academic Press, London
- Breviario F, d’Aniello EM, Golay J, Peri G, Bottazzi B, Bairoch A, Saccone S, Marzella R, Predazzi V, Rocchi M: Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. J Biol Chem 1992, 267:22190-22197 - PubMed
- Sankary HN, Yin DP, Chong AS, Ma LL, Blinder L, Shen JK, Foster P, Liu LP, Li C, Williams JW: The portosystemic shunt protects liver against ischemic reperfusion injury. Transplantation 1999, 68:958-963 - PubMed
- Lee GW, Lee TH, Vilcek J: TSG-14, a tumor necrosis factor- and IL-1-inducible protein, is a novel member of the pentaxin family of acute phase proteins. J Immunol 1993, 150:1804-1812 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous