Activation of Natural Killer T Cells Ameliorates Postinfarct Cardiac Remodeling and Failure in Mice

作者：Sobirin Mochamad Ali; Kinugawa Shintaro^*; Takahashi Masashige; Fukushima Arata; Homma Tsuneaki; Ono Taisuke; Hirabayashi Kagami; Suga Tadashi; Azalia Putri; Takada Shingo; Taniguchi Masaru; Nakayama Toshinori; Ishimori Naoki; Iwabuchi Kazuya; Tsutsui Hiroyuki

来源：Circulation Research, 2012, 111(8): 1037-+.

DOI：10.1161/CIRCRESAHA.112.270132

• natural killer T cells
• myocardial infarction
• inflammation
• heart failure
• cytokines

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. %26lt;br%26gt;Objective: The purpose of this study was to examine whether the activation of iNKT cells might affect the development of LV remodeling and failure. %26lt;br%26gt;Methods and Results: After creation of MI, mice received the injection of either alpha-galactosylceramide (alpha GC; n=27), the activator of iNKT cells, or phosphate-buffered saline (n=31) 1 and 4 days after surgery, and were followed during 28 days. Survival rate was significantly higher in MI+alpha GC than MI+PBS (59% versus 32%, P%26lt;0.05). LV cavity dilatation and dysfunction were significantly attenuated in MI+alpha GC, 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 noninfarcted LV from MI and alpha GC further enhanced them. It also enhanced LV interleukin (IL)-10 gene expression at 7 days, which persisted until 28 days. AntienIL-10 receptor antibody abrogated these protective effects of alpha GC on MI remodeling. The administration of alpha GC into iNKT cell-deficient J alpha 18(-/-) mice had no such effects, suggesting that alpha GC was a specific activator of iNKT cells. %26lt;br%26gt;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. (Circ Res. 2012;111:1037-1047.)

• 出版日期2012-9-28