| First Author | Dawn B | Year | 2004 |
| Journal | Cardiovasc Res | Volume | 64 |
| Issue | 1 | Pages | 61-71 |
| PubMed ID | 15364614 | Mgi Jnum | J:162844 |
| Mgi Id | MGI:4820435 | Doi | 10.1016/j.cardiores.2004.05.011 |
| Citation | Dawn B, et al. (2004) IL-6 plays an obligatory role in late preconditioning via JAK-STAT signaling and upregulation of iNOS and COX-2. Cardiovasc Res 64(1):61-71 |
| abstractText | OBJECTIVE: We sought to determine whether interleukin (IL)-6 modulates myocardial infarction or the late phase of preconditioning (PC). METHODS: Wild-type and IL-6(-/-) mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion with or without six cycles of coronary occlusion/reperfusion 24 h earlier. Myocardial IL-6 protein expression, activation of Janus kinase (JAK) 1 and JAK2, and signal transducers and activators of transcription (STAT) 1 and STAT3 after ischemic PC protocol were examined. The expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was determined 24 h after the PC ischemia. RESULTS: In preconditioned wild-type mice, infarct size was reduced from 60.5+/-2.6% of the risk region to 33.5+/-3.6%, indicating a late PC effect. In nonpreconditioned IL-6(-/-) mice, infarct size was similar to that observed in wild-type mice (59.9+/-3.8%), indicating that the deletion of IL-6 has no effect on infarct size. However, in preconditioned IL-6(-/-) mice, infarct size was not reduced (65.1+/-3.1%), indicating that the infarct-sparing effect was completely abrogated. Ischemic PC increased the expression of IL-6 in the cytoplasm of cardiomyocytes in the ischemic/reperfused zone. In IL-6(-/-) mice, the ischemic PC-induced activation of JAK1 and JAK2 and STAT1 and STAT3 was significantly reduced, and the increase in iNOS and COX-2 protein expression 24 h after the PC ischemia was markedly attenuated. CONCLUSION: IL-6 does not modulate myocardial infarct size in naive myocardium. However, following a PC stimulus, IL-6 is obligatorily required for the activation of the JAK-STAT pathway, the ensuing upregulation of iNOS and COX-2 (co-mediators of late PC), and the development of a cardioprotective phenotype. |
