Tim-3 cell signaling and iNOS are involved in the protective effects of ischemic postconditioning against focal ischemia in rats.
The protective effect of ischemic postconditioning (IPostC) against stroke has been well-established, and the underlying mechanisms are known to involve inhibited-inflammation and free radical production. Nevertheless, how IPostC affects protein expression of iNOS, nitrotyrosine, and COX-2 has not been characterized. In addition, the role of the galectin-9/Tim-3 cell signaling pathway--a novel inflammatory pathway--in IPostC has not been studied. We examined whether iNOS, nitrotyrosine, and COX-2, as well as galectin-9/Tim-3 are involved in the protective effects of IpostC in a rat focal ischemia model. Western blot and confocal immunofluoresent staining results indicate that IPostC significantly inhibited Tim-3 expression, and that galectin-9 expression was also inhibited. In addition, IPostC attenuated production of iNOS and nitrotyrosine, but not COX-2, suggesting that IPostC has distinct effects on these inflammatory factors. Furthermore, the inflammation inhibitor minocycline blocked Tim-3 and iNOS expression induced by stroke. Taken together, we show that the galectin-9/Tim-3 cell signaling pathway is involved in inflammation induced by stroke, and IPostC may reduce infarction by attenuating this novel pathway as well as the inflammatory factors iNOS and nitrotyrosine, but not COX-2.
Department of Neurosurgery, Stanford University School of Medicine, MSLS Bldg., Room P306, 1201 Welch Rd, Stanford, CA, 94305-5327, USA.
Dingtai
D
Wei
Xiaoxing
X
Xiong
Heng
H
Zhao
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002545:Brain Ischemia / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D057775:Ischemic Postconditioning; D008297:Male; D008911:Minocycline / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000893:Anti-Inflammatory Agents; C569429:Havcr2 protein, rat; D011956:Receptors, Cell Surface; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D008911:Minocycline