Activation of invariant natural killer T cells by α-galactosylceramide ameliorates myocardial ischemia/reperfusion injury in mice

Tsuneaki Homma, Shintaro Kinugawa, Masashige Takahashi, Mochamad Ali Sobirin, Akimichi Saito, Arata Fukushima, Tadashi Suga, Shingo Takada, Tomoyasu Kadoguchi, Yoshihiro Masaki, Takaaki Furihata, Masaru Taniguchi, Toshinori Nakayama, Naoki Ishimori, Kazuya Iwabuchi, Hiroyuki Tsutsui

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42 Citations (Scopus)


Invariant natural killer T (iNKT) cells orchestrate tissue inflammation via regulating various cytokine productions. However the role of iNKT cells has not been determined in myocardial ischemia/reperfusion (I/R) injury. The purpose of this study was to examine whether the activation of iNKT cells by α-galactosylceramide (α-GC), which specifically activates iNKT cells, could affect myocardial I/R injury. I/R or sham operation was performed in male C57BL/6J mice. I/R mice received the injection of either αGC (I/R. +. αGC, n. = 48) or vehicle (I/R. +. vehicle, n. = 49) 30. min before reperfusion. After 24. h, infarct size/area at risk was smaller in I/R. +. αGC than in I/R. +. vehicle (37.8. ±. 2.7% vs. 47.1. ±. 2.5%, P<. 0.05), with no significant changes in area at risk. The numbers of infiltrating myeloperoxidase- and CD3-positive cells were lower in I/R. +. αGC. Apoptosis evaluated by TUNEL staining and caspase-3 protein was also attenuated in I/R. +. αGC. Myocardial gene expression of tumor necrosis factor-α and interleukin (IL)-1β in I/R. +. αGC was lower to 46% and 80% of that in I/R. +. vehicle, respectively, whereas IL-10, IL-4, and interferon (IFN)-γ were higher in I/R. +. αGC than I/R. +. vehicle by 2.0, 4.1, and 9.6 folds, respectively. The administration of anti-IL-10 receptor antibody into I/R. +. αGC abolished the protective effects of αGC on I/R injury (infarct size/area at risk: 53.1. ±. 5.2% vs. 37.4. ±. 3.5%, P<. 0.05). In contrast, anti-IL-4 and anti-IFN-γ antibodies did not exert such effects. In conclusion, activated iNKT cells by αGC play a protective role against myocardial I/R injury through the enhanced expression of IL-10. Therapies designed to activate iNKT cells might be beneficial to protect the heart from I/R injury.

Original languageEnglish
Pages (from-to)179-188
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Publication statusPublished - Sept 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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