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Inflammatory Response In The Small Intestine Induced By Hind Limb Ischemia/Reperfusion (I/R): Role of iNOS
Author(s) -
Katada Kazuhiro,
Bihari Aurelia,
Sun Big Wei,
Harris Kenneth A.,
Potter Richard F.,
Cepinskas Gediminas
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1083-d
Subject(s) - hindlimb , jejunum , duodenum , ileum , small intestine , western blot , medicine , endocrinology , myeloperoxidase , chemistry , ischemia , inflammation , biology , biochemistry , gene
Systemic inflammatory response negatively affects the function of many organs. In this study we assessed the mechanisms of remote intestinal inflammatory response elicited by hind limb I/R. To this end C57BL/6 mice were subjected to 1h of bilateral hind limb ischemia followed by 6h of reperfusion. Some mice were injected (s.c.) with iNOS inhibitor, 1400W (5mg/kg) immediately before induction of ischemia. The obtained results indicate that hind limb I/R results in dysfunction of the gut as assessed by the increased levels of protein in the lumen of small intestine. Also, there was a significant increase in TNF‐α protein in the luminal samples. In addition, hind limb I/R resulted in an increase in PMN accumulation (index of inflammation; MPO assay) in the small intestine. Important to note, that the highest MPO activity was found in duodenum in comparison to MPO levels in jejunum and ileum. On the contrary, induction of iNOS and inducible heme oxygenase (HO‐1) at the protein level (Western blot) was most notable in jejunum and ileum, whereas both proteins were undetectable in duodenum. Interfering with iNOS activity (1400W) significantly attenuated the total and TNF‐α protein levels in the gut lumen, and reduced PMN accumulation in duodenum. While inhibition of iNOS had no effect on iNOS expression in the small intestine, at the same time up‐regulation of HO‐1 in jejunum and ileum in response to hind limb I/R was significantly down‐regulated in 1400W‐treated mice. Taken together these data indicate that hind limb I/R induces remote inflammatory response in the small intestine. iNOS‐derived NO plays and important role in this phenomenon (HSFO‐NA5580 and MOP‐68848)