| Title: | Activation of Natural Killer T Cells Ameliorates Postinfarct Cardiac Remodeling and Failure in Mice |
| Authors: | Sobirin, Mochamad Ali Browse this author |
| Kinugawa, Shintaro Browse this author →KAKEN DB |
| Takahashi, Masashige Browse this author |
| Fukushima, Arata Browse this author →KAKEN DB |
| Homma, Tsuneaki Browse this author |
| Ono, Taisuke Browse this author |
| Hirabayashi, Kagami Browse this author |
| Suga, Tadashi Browse this author →KAKEN DB |
| Azalia, Putri Browse this author |
| Takada, Shingo Browse this author →KAKEN DB |
| Taniguchi, Masaru Browse this author →KAKEN DB |
| Nakayama, Toshinori Browse this author →KAKEN DB |
| Ishimori, Naoki Browse this author →KAKEN DB |
| Iwabuchi, Kazuya Browse this author →KAKEN DB |
| Tsutsui, Hiroyuki Browse this author →KAKEN DB |
| Keywords: | natural killer T cells |
| myocardial infarction |
| inflammation |
| heart failure |
| cytokines |
| Issue Date: | 28-Sep-2012 |
| Publisher: | American Heart Association |
| Journal Title: | Circulation Research |
| Volume: | 111 |
| Issue: | 8 |
| Start Page: | 1037 |
| End Page: | 1047 |
| Publisher DOI: | 10.1161/CIRCRESAHA.112.270132 |
| PMID: | 22887770 |
| Abstract: | Rationale: Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies have determined the pathophysiological role of iNKT cells in post-MI LV remodeling. Objective: The purpose of this study was to examine whether the activation of iNKT cells might affect the development of LV remodeling and failure. Methods and Results: After creation of MI, mice received the injection of either α-galactosylceramide (αGC; n=27), the activator of iNKT cells, or phosphate-buffered saline (PBS; n=31) 1 and 4 days after surgery, and were followed during 28 days. Survival rate was significantly higher in MI+αGC than MI+PBS (59% vs 32%, P<0.05). LV cavity dilatation and dysfunction were significantly attenuated in MI+αGC, despite comparable infarct size, accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis. The infiltration of iNKT cells were increased during early phase in non-infarcted LV from MI and αGC further enhanced them. It also enhanced LV interleukin (IL)-10 gene expression at 7 days, which persisted until 28 days. Anti IL-10 receptor antibody abrogated these protective effects of αGC on MI remodeling. The administration of αGC into iNKT cell-deficient Jα18^[-/-] mice had no such effects, suggesting that αGC was a specific activator of iNKT cells. Conclusions: iNKT cells play a protective role against post-MI LV remodeling and failure through the enhanced expression of cardioprotective cytokines such as IL-10. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/52273 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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