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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cardiology and Cardiovascular Medicine