title: Activation of natural killer T cells ameliorates postinfarct cardiac remodeling and failure in mice.
abstract: BACKGROUND
  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.
  
  
  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 (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% versus 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 noninfarcted 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. AntienIL-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.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo Faculty of Medicine, Sapporo, Japan.
authors.forename: Mochamad Ali
authors.initials: MA
authors.lastname: Sobirin
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kinugawa
authors.forename: Masashige
authors.initials: M
authors.lastname: Takahashi
authors.forename: Arata
authors.initials: A
authors.lastname: Fukushima
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Homma
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ono
authors.forename: Kagami
authors.initials: K
authors.lastname: Hirabayashi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Suga
authors.forename: Putri
authors.initials: P
authors.lastname: Azalia
authors.forename: Shingo
authors.initials: S
authors.lastname: Takada
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishimori
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D006439:Hemodynamics / Q000502:physiology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009929:Organ Size; D020257:Ventricular Remodeling / Q000276:immunology*
chemical_list: D015415:Biomarkers; C556062:IL10 protein, mouse; D016753:Interleukin-10