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. 2001 May;48(5):610–622. doi: 10.1136/gut.48.5.610

Absence of endogenous interleukin 10 enhances early stress response during post-ischaemic injury in mice intestine

B Zingarelli 1, Z Yang 1, P Hake 1, A Denenberg 1, H Wong 1
PMCID: PMC1728281  PMID: 11302957

Abstract

BACKGROUND—Interleukin 10 (IL-10) exerts a wide spectrum of regulatory activities in immune and inflammatory responses.
AIMS—The aim of this study was to investigate the role of endogenous IL-10 on modulation of the early inflammatory response after splanchnic ischaemia and reperfusion.
METHODS—Intestinal damage was induced by clamping the superior mesenteric artery and the coeliac trunk for 45 minutes followed by reperfusion in IL-10 deficient mice (IL-10−/−) and wild-type controls.
RESULTS—IL-10−/− mice experienced a higher rate of mortality and more severe tissue injury compared with wild-type mice subjected to ischaemia and reperfusion. Splanchnic injury was characterised by massive epithelial haemorrhagic necrosis, upregulation of P-selectin and intercellular adhesion molecule 1, and neutrophil infiltration. The degree of oxidative and nitrosative damage was significantly higher in IL-10−/− mice than in wild-type littermates, as indicated by elevated malondialdehyde levels and formation of nitrotyrosine. Plasma levels of the proinflammatory cytokines tumour necrosis factor α and interleukin 6 were also greatly enhanced in comparison with wild-type mice. These events were preceded by increased immunostaining and activity of the stress regulated c-Jun NH2 terminal kinase and activation of the transcription factor activator protein 1 in the cellular nuclei of damaged tissue.
CONCLUSIONS—These data demonstrate that endogenous IL-10 exerts an anti-inflammatory role during reperfusion injury, possibly by regulating early stress related genetic response, adhesion molecule expression, neutrophil recruitment, and subsequent cytokine and oxidant generation.


Keywords: splanchnic tissue; activator protein 1; adhesion molecules; interleukin 6; c-Jun NH2 terminal kinase; tumour necrosis factor α

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Figure 1  .

Figure 1  

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Survival is significantly improved in interleukin 10 (IL-10)+/+ mice subjected to splanchnic ischaemia and reperfusion in comparison with the high mortality rate of IL-10−/− mice. (A) Survival was monitored for four hours after severe reperfusion injury was induced by clamping the superior mesenteric artery and coeliac trunk for 45 minutes. (B) Survival was monitored for four hours after a mild reperfusion injury was induced by clamping only the superior mesenteric artery for 45 minutes. Each point represents percentage of survivors (n=12 animals for each group). *Significantly different from IL-10+/+ mice (p<0.05).

Figure 2  .

Figure 2  

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Representative splanchnic sections from sham operated interleukin 10 (IL-10)+/+ (A) or IL-10−/− (B) animals showed normal tissue structure. Following 45 minutes of occlusion and 45 minutes of reperfusion of the superior mesenteric artery and coeliac trunk (I-R), epithelial disruption was demonstrated in ileal sections from IL-10+/+ mice (C). In IL-10−/− mice subjected to I-R, the splanchnic architecture appeared markedly altered, characterised by the appearance of extensive necrosis, haemorrhage, and neutrophil infiltrate (D). Magnification ×100. A similar pattern was seen in 5-6 different tissue sections in each experimental group.

Figure 3  .

Figure 3  

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Effect of genetic absence of interleukin 10 (IL-10) on myeloperoxidase activity (A), score of immunostaining for P-selectin (B), and score of immunostaining for intercellular adhesion molecule 1 (ICAM-1) (C). Tissue myeloperoxidase activity was enhanced together with increased staining for P-selectin and ICAM-1 after reperfusion in IL-10+/+ mice subjected to splanchnic ischaemia and reperfusion (I-R). In IL-10−/− mice subjected to splanchnic injury, levels of myeloperoxidase, and staining for P-selectin and ICAM-1 were significantly higher compared with IL-10+/+ animals (*p<0.05 v respective sham; †p<0.05 v IL-10+/+ mice). Each point is mean (SEM) of six animals in each group.

Figure 4  .

Figure 4  

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Representative immunostaining of intestinal expression of P-selectin. Sections from the small intestine of sham operated interleukin 10 (IL-10)+/+ (A) or IL-10−/− animals (B) had no P-selectin staining. Splanchnic ischaemia and reperfusion (I-R) in IL-10+/+ animals induced the appearance of positive staining for P-selectin (arrows) along the endothelium in the small vessels of the lamina propria (C). In IL-10−/− mice subjected to I-R, immunostaining for P-selectin was markedly enhanced (D). Magnification ×400. A similar pattern was seen in n=5-6 different tissue sections in each experimental group.

Figure 5  .

Figure 5  

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Representative immunostaining of intestinal expression of intercellular adhesion molecule 1 (ICAM-1). Control tissues from sham operated interleukin 10 (IL-10)+/+ (A) or IL-10−/− animals (B) showed a dark brown staining (arrows) of endothelium of blood vessels indicating the presence of constitutive ICAM-1 protein. Splanchnic ischaemia and reperfusion (I-R) in IL-10+/+ induced an increase in positive staining for ICAM-1 along the endothelial vascular wall and also in the injured epithelium (arrows) (C). In IL-10−/− mice subjected to I-R, immunostaining for ICAM-1 was markedly enhanced in the endothelium, damaged epithelial cells, and infiltrated inflammatory cells (arrows) (D). Magnification ×400. A similar pattern was seen in n=5-6 different tissue sections in each experimental group. ICAM-1 was identified by immunohistochemical localisation with specific antibody labelling using an avidin-biotin peroxidase technique.

Figure 6  .

Figure 6  

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Effect of genetic absence of interleukin 10 (IL-10) on tissue levels of malondialdehyde (A) and score of immunostaining for nitrotyrosine (B). Tissue malondialdehyde was enhanced together with increased staining for nitrotyrosine after reperfusion in IL-10+/+ mice subjected to splanchnic ischaemia (I-R). In IL-10−/− mice subjected to splanchnic injury, levels of malondialdehyde and staining for nitrotyrosine were significantly higher compared with IL-10+/+ animals (*p<0.05 v respective sham; †p<0.05 v IL-10+/+ mice). Each point is the mean (SEM) of six animals in each group.

Figure 7  .

Figure 7  

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Representative immunostaining of intestinal nitrotyrosine. Immunohistochemical staining of nitrotyrosine was considered as a marker of nitrosative stress. In sections of small intestine from sham operated interleukin 10 (IL-10)+/+ (A) or IL-10−/− animals (B), weak non-specific or no staining for nitrotyrosine was found. In the reperfused splanchnic tissue after ischaemia (SAO) of IL-10+/+ animals a diffuse dark staining was localised in the necrotic area (C). In IL-10−/− mice subjected to SAO, immunostaining for nitrotyrosine was markedly enhanced (D). Magnification ×100. A similar pattern was seen in n=5-6 different tissue sections in each experimental group.

Figure 8  .

Figure 8  

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Effect of genetic absence of interleukin 10 (IL-10) on IL-10, tumour necrosis factor α (TNF-α), and interleukin 6 (IL-6) production after splanchnic ischaemia and reperfusion (I-R). Each point is the mean (SEM) of five animals in each group (*p<0.05 v respective sham; †p<0.05 v IL-10+/+ mice).

Figure 9  .

Figure 9  

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Effect of genetic absence of interleukin 10 (IL-10) on activation of activator protein 1 (AP-1) during splanchnic ischaemia and reperfusion. (A) Representative autoradiograph of electrophoretic mobility shift assay for AP-1. Lane 1 represents intestinal basal DNA binding activity of AP-1 of a wild-type mouse at time 0; lanes 2-3 show slightly increased activity in splanchnic sections from wild-type mice at 45 minutes of ischaemia (lane 2), and at reperfusion at five minutes (lane 3); decline of activity was seen at reperfusion at 15 (lane 4), 30(lane 5), and 45(lane 6) minutes; lane 7 represents intestinal basal DNA binding activity of AP-1 of a IL-10−/− mouse at time 0; lanes 8-11 show marked upregulation of nuclear activity at 45 minutes of ischaemia (lane 8), and at reperfusion at five (lane 9), 15 (lane 10), and 30 (lane 11) minutes in IL-10−/− mice; and decline of activity was seen at 45 minutes of reperfusion (lane 12). (B) Image analysis of activation of AP-1 determined by densitometry from the autoradiograph. Fold increase was calculated versus respective sham value (time 0) set to 1.0. Results are representative of three separate time course experiments.

Figure 10  .

Figure 10  

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Representative immunostaining of c-Jun NH2 terminal kinase (JNK1) after splanchnic ischaemia and reperfusion. JNK1 was absent in splanchnic sections from sham wild-type (A) and interleukin 10 (IL-10)−/− (B) mice. After ischaemia and reperfusion (I-R), marked positive staining was demonstrated in the nuclei (arrowheads) and cytoplasm (arrows) of splanchnic sections from IL-10+/+ mice (C-E). Positive staining for JNK1 was markedly increased in the cytoplasm (arrowheads) and nuclei (arrows) of splanchnic sections from IL-10−/− mice subjected to I-R (D-F). Magnification ×1000 (A-D) and ×2000 (E, F). A similar pattern was seen in n=5-6 different tissue sections in each experimental group. JNK1 was identified by immunohistochemical localisation with specific antibody labelling using an avidin-biotin peroxidase technique.

Figure 11  .

Figure 11  

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(A) Representative immunoblot of activation of c-Jun NH2 terminal kinase (JNK1) in small intestine during ischaemia (45 minutes) and reperfusion (up to 45 minutes) of the superior mesenteric artery and coeliac trunk in interleukin 10 (IL-10)−/− and wild-type IL-10+/+ mice. Lane 1 represents intestinal basal JNK1 activity in nuclear extracts of a wild-type mouse at time 0; lanes 2-6 show JNK1 activity in splanchnic sections from wild-type mice at 45 minutes of ischaemia (lane 2), and at reperfusion at five (lane 3), 15 (lane 4), 30 (lane 5), and 45 (lane 6) minutes; lane 7 represents intestinal basal JNK1 activity of a IL-10−/− mouse at time 0; lane 8 represents JNK1 activity of a IL-10−/− mouse at 45 minutes of ischaemia; and lanes 9-12 show marked upregulation of nuclear activity at reperfusion at five (lane 9), 15 (lane 10), 30 (lane 11), and 45 (lane 12) minutes in IL-10−/− mice. (B) Amounts of JNK1 activity (fold increase versus respective sham value set to 1.0) were determined by densitometry from the immunoblot. JNK1 activity was estimated as the ability to phosphorylate glutathione-S-transferase (GST)-c-Jun after immunoprecipitation of nuclear proteins with specific anti-JNK1 antibody.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arrigo A. P. Gene expression and the thiol redox state. Free Radic Biol Med. 1999 Nov;27(9-10):936–944. doi: 10.1016/s0891-5849(99)00175-6. [DOI] [PubMed] [Google Scholar]
  2. Beckman J. S. Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol. 1996 Jul-Aug;9(5):836–844. doi: 10.1021/tx9501445. [DOI] [PubMed] [Google Scholar]
  3. Bogdan C., Vodovotz Y., Nathan C. Macrophage deactivation by interleukin 10. J Exp Med. 1991 Dec 1;174(6):1549–1555. doi: 10.1084/jem.174.6.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cappell M. S. Intestinal (mesenteric) vasculopathy. I. Acute superior mesenteric arteriopathy and venopathy. Gastroenterol Clin North Am. 1998 Dec;27(4):783-825, vi. doi: 10.1016/s0889-8553(05)70033-9. [DOI] [PubMed] [Google Scholar]
  5. Cuzzocrea S., Zingarelli B., Costantino G., Szabó A., Salzman A. L., Caputi A. P., Szabó C. Beneficial effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase in a rat model of splanchnic artery occlusion and reperfusion. Br J Pharmacol. 1997 Jul;121(6):1065–1074. doi: 10.1038/sj.bjp.0701234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Daemen M. A., van de Ven M. W., Heineman E., Buurman W. A. Involvement of endogenous interleukin-10 and tumor necrosis factor-alpha in renal ischemia-reperfusion injury. Transplantation. 1999 Mar 27;67(6):792–800. doi: 10.1097/00007890-199903270-00003. [DOI] [PubMed] [Google Scholar]
  7. Davenpeck K. L., Gauthier T. W., Albertine K. H., Lefer A. M. Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion. Am J Physiol. 1994 Aug;267(2 Pt 2):H622–H630. doi: 10.1152/ajpheart.1994.267.2.H622. [DOI] [PubMed] [Google Scholar]
  8. Davis R. J. Signal transduction by the c-Jun N-terminal kinase. Biochem Soc Symp. 1999;64:1–12. doi: 10.1515/9781400865048.1. [DOI] [PubMed] [Google Scholar]
  9. Eiserich J. P., Cross C. E., Jones A. D., Halliwell B., van der Vliet A. Formation of nitrating and chlorinating species by reaction of nitrite with hypochlorous acid. A novel mechanism for nitric oxide-mediated protein modification. J Biol Chem. 1996 Aug 9;271(32):19199–19208. doi: 10.1074/jbc.271.32.19199. [DOI] [PubMed] [Google Scholar]
  10. Eiserich J. P., Hristova M., Cross C. E., Jones A. D., Freeman B. A., Halliwell B., van der Vliet A. Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature. 1998 Jan 22;391(6665):393–397. doi: 10.1038/34923. [DOI] [PubMed] [Google Scholar]
  11. Engles R. E., Huber T. S., Zander D. S., Hess P. J., Welborn M. B., Moldawer L. L., Seeger J. M. Exogenous human recombinant interleukin-10 attenuates hindlimb ischemia-reperfusion injury. J Surg Res. 1997 May;69(2):425–428. doi: 10.1006/jsre.1997.5109. [DOI] [PubMed] [Google Scholar]
  12. Gilad E., Wong H. R., Zingarelli B., Virág L., O'Connor M., Salzman A. L., Szabó C. Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: role of inhibition of NFkappaB activation. FASEB J. 1998 Jun;12(9):685–693. doi: 10.1096/fasebj.12.9.685. [DOI] [PubMed] [Google Scholar]
  13. Gudmundsson G., Bosch A., Davidson B. L., Berg D. J., Hunninghake G. W. Interleukin-10 modulates the severity of hypersensitivity pneumonitis in mice. Am J Respir Cell Mol Biol. 1998 Nov;19(5):812–818. doi: 10.1165/ajrcmb.19.5.3153. [DOI] [PubMed] [Google Scholar]
  14. Gupta S., Campbell D., Dérijard B., Davis R. J. Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science. 1995 Jan 20;267(5196):389–393. doi: 10.1126/science.7824938. [DOI] [PubMed] [Google Scholar]
  15. Gérard C., Bruyns C., Marchant A., Abramowicz D., Vandenabeele P., Delvaux A., Fiers W., Goldman M., Velu T. Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J Exp Med. 1993 Feb 1;177(2):547–550. doi: 10.1084/jem.177.2.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Halliwell B. What nitrates tyrosine? Is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo? FEBS Lett. 1997 Jul 14;411(2-3):157–160. doi: 10.1016/s0014-5793(97)00469-9. [DOI] [PubMed] [Google Scholar]
  17. Hayward R., Lefer A. M. Time course of endothelial-neutrophil interaction in splanchnic artery ischemia-reperfusion. Am J Physiol. 1998 Dec;275(6 Pt 2):H2080–H2086. doi: 10.1152/ajpheart.1998.275.6.H2080. [DOI] [PubMed] [Google Scholar]
  18. Hayward R., Nossuli T. O., Scalia R., Lefer A. M. Cardioprotective effect of interleukin-10 in murine myocardial ischemia-reperfusion. Eur J Pharmacol. 1997 Sep 10;334(2-3):157–163. doi: 10.1016/s0014-2999(97)01149-7. [DOI] [PubMed] [Google Scholar]
  19. Hess P. J., Seeger J. M., Huber T. S., Welborn M. B., Martin T. D., Harward T. R., Duschek S., Edwards P. D., Solorzano C. C., Copeland E. M. Exogenously administered interleukin-10 decreases pulmonary neutrophil infiltration in a tumor necrosis factor-dependent murine model of acute visceral ischemia. J Vasc Surg. 1997 Jul;26(1):113–118. doi: 10.1016/s0741-5214(97)70154-x. [DOI] [PubMed] [Google Scholar]
  20. Hickey M. J., Issekutz A. C., Reinhardt P. H., Fedorak R. N., Kubes P. Endogenous interleukin-10 regulates hemodynamic parameters, leukocyte-endothelial cell interactions, and microvascular permeability during endotoxemia. Circ Res. 1998 Nov 30;83(11):1124–1131. doi: 10.1161/01.res.83.11.1124. [DOI] [PubMed] [Google Scholar]
  21. Horie Y., Wolf R., Miyasaka M., Anderson D. C., Granger D. N. Leukocyte adhesion and hepatic microvascular responses to intestinal ischemia/reperfusion in rats. Gastroenterology. 1996 Sep;111(3):666–673. doi: 10.1053/gast.1996.v111.pm8780571. [DOI] [PubMed] [Google Scholar]
  22. Karin M., Liu Z. g., Zandi E. AP-1 function and regulation. Curr Opin Cell Biol. 1997 Apr;9(2):240–246. doi: 10.1016/s0955-0674(97)80068-3. [DOI] [PubMed] [Google Scholar]
  23. Knoblach S. M., Faden A. I. Interleukin-10 improves outcome and alters proinflammatory cytokine expression after experimental traumatic brain injury. Exp Neurol. 1998 Sep;153(1):143–151. doi: 10.1006/exnr.1998.6877. [DOI] [PubMed] [Google Scholar]
  24. Krawisz J. E., Sharon P., Stenson W. F. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology. 1984 Dec;87(6):1344–1350. [PubMed] [Google Scholar]
  25. Kühn R., Löhler J., Rennick D., Rajewsky K., Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993 Oct 22;75(2):263–274. doi: 10.1016/0092-8674(93)80068-p. [DOI] [PubMed] [Google Scholar]
  26. Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
  27. Lentsch A. B., Shanley T. P., Sarma V., Ward P. A. In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13. J Clin Invest. 1997 Nov 15;100(10):2443–2448. doi: 10.1172/JCI119786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Madsen K. L., Doyle J. S., Jewell L. D., Tavernini M. M., Fedorak R. N. Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology. 1999 May;116(5):1107–1114. doi: 10.1016/s0016-5085(99)70013-2. [DOI] [PubMed] [Google Scholar]
  29. Mesri M., Altieri D. C. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem. 1999 Aug 13;274(33):23111–23118. doi: 10.1074/jbc.274.33.23111. [DOI] [PubMed] [Google Scholar]
  30. Mizukami Y., Yoshioka K., Morimoto S., Yoshida K. i. A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion. J Biol Chem. 1997 Jun 27;272(26):16657–16662. doi: 10.1074/jbc.272.26.16657. [DOI] [PubMed] [Google Scholar]
  31. Moore K. W., O'Garra A., de Waal Malefyt R., Vieira P., Mosmann T. R. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. doi: 10.1146/annurev.iy.11.040193.001121. [DOI] [PubMed] [Google Scholar]
  32. Morise Z., Eppihimer M., Granger D. N., Anderson D. C., Grisham M. B. Effects of lipopolysaccharide on endothelial cell adhesion molecule expression in interleukin-10 deficient mice. Inflammation. 1999 Apr;23(2):99–110. doi: 10.1023/a:1020232826906. [DOI] [PubMed] [Google Scholar]
  33. Ohkawa H., Ohishi N., Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979 Jun;95(2):351–358. doi: 10.1016/0003-2697(79)90738-3. [DOI] [PubMed] [Google Scholar]
  34. Onishi I., Shimizu K., Tani T., Hashimoto T., Miwa K. JNK activation and apoptosis during ischemia-reperfusion. Transplant Proc. 1999 Feb-Mar;31(1-2):1077–1079. doi: 10.1016/s0041-1345(98)01912-5. [DOI] [PubMed] [Google Scholar]
  35. Panés J., Granger D. N. Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease. Gastroenterology. 1998 May;114(5):1066–1090. doi: 10.1016/s0016-5085(98)70328-2. [DOI] [PubMed] [Google Scholar]
  36. Riley J. K., Takeda K., Akira S., Schreiber R. D. Interleukin-10 receptor signaling through the JAK-STAT pathway. Requirement for two distinct receptor-derived signals for anti-inflammatory action. J Biol Chem. 1999 Jun 4;274(23):16513–16521. doi: 10.1074/jbc.274.23.16513. [DOI] [PubMed] [Google Scholar]
  37. Roebuck K. A., Rahman A., Lakshminarayanan V., Janakidevi K., Malik A. B. H2O2 and tumor necrosis factor-alpha activate intercellular adhesion molecule 1 (ICAM-1) gene transcription through distinct cis-regulatory elements within the ICAM-1 promoter. J Biol Chem. 1995 Aug 11;270(32):18966–18974. doi: 10.1074/jbc.270.32.18966. [DOI] [PubMed] [Google Scholar]
  38. Santucci L., Fiorucci S., Chiorean M., Brunori P. M., Di Matteo F. M., Sidoni A., Migliorati G., Morelli A. Interleukin 10 reduces lethality and hepatic injury induced by lipopolysaccharide in galactosamine-sensitized mice. Gastroenterology. 1996 Sep;111(3):736–744. doi: 10.1053/gast.1996.v111.pm8780580. [DOI] [PubMed] [Google Scholar]
  39. Song J. S., Haleem-Smith H., Arudchandran R., Gomez J., Scott P. M., Mill J. F., Tan T. H., Rivera J. Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway. J Immunol. 1999 Jul 15;163(2):802–810. [PubMed] [Google Scholar]
  40. Spera P. A., Ellison J. A., Feuerstein G. Z., Barone F. C. IL-10 reduces rat brain injury following focal stroke. Neurosci Lett. 1998 Jul 31;251(3):189–192. doi: 10.1016/s0304-3940(98)00537-0. [DOI] [PubMed] [Google Scholar]
  41. Wang P., Wu P., Siegel M. I., Egan R. W., Billah M. M. Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J Biol Chem. 1995 Apr 21;270(16):9558–9563. doi: 10.1074/jbc.270.16.9558. [DOI] [PubMed] [Google Scholar]
  42. Yang Z., Zingarelli B., Szabó C. Crucial role of endogenous interleukin-10 production in myocardial ischemia/reperfusion injury. Circulation. 2000 Mar 7;101(9):1019–1026. doi: 10.1161/01.cir.101.9.1019. [DOI] [PubMed] [Google Scholar]
  43. Yoshidome H., Kato A., Edwards M. J., Lentsch A. B. Interleukin-10 suppresses hepatic ischemia/reperfusion injury in mice: implications of a central role for nuclear factor kappaB. Hepatology. 1999 Jul;30(1):203–208. doi: 10.1002/hep.510300120. [DOI] [PubMed] [Google Scholar]
  44. Zingarelli B., Salzman A. L., Szabó C. Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res. 1998 Jul 13;83(1):85–94. doi: 10.1161/01.res.83.1.85. [DOI] [PubMed] [Google Scholar]
  45. Zingarelli B., Squadrito F., Ioculano M., Altavilla D., Bussolino F., Campo G. M., Caputi A. P. Platelet activating factor interaction with tumor necrosis factor and myocardial depressant factor in splanchnic artery occlusion shock. Eur J Pharmacol. 1992 Nov 3;222(1):13–19. doi: 10.1016/0014-2999(92)90456-e. [DOI] [PubMed] [Google Scholar]
  46. Zingarelli B., Szabó C., Salzman A. L. Blockade of Poly(ADP-ribose) synthetase inhibits neutrophil recruitment, oxidant generation, and mucosal injury in murine colitis. Gastroenterology. 1999 Feb;116(2):335–345. doi: 10.1016/s0016-5085(99)70130-7. [DOI] [PubMed] [Google Scholar]

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