کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5665265 | 1407739 | 2017 | 7 صفحه PDF | دانلود رایگان |
BackgroundInterleukin-33 (IL-33) is an alarmin cytokine that binds to the interleukin 1 receptor-like 1 protein ST2. Clock is a key circadian gene that is essential for endogenous clockworks in mammals. This study investigated whether Clock temporally regulated IL-33-mediated responses in mast cells.MethodsThe kinetics of IL-33-mediated IL-6, IL-13, and TNF-α productions were compared between bone marrow-derived mast cells (BMMCs) from wild-type and Clock-mutated mice (ClockÎ19/Î19 mice). The kinetics of the neutrophil influx into the peritoneal cavity or expression of IL-13 and Gob-5 in the lung in response to IL-33 were compared between wild-type and ClockÎ19/Î19 mice. We also examined the kinetics of ST2 expression in mast cells and its association with Clock expression.ResultsThere was a time-of-day-dependent variation in IL-33-mediated IL-6, IL-13, and TNF-α production in wild-type BMMCs, which was absent in Clock-mutated BMMCs. IL-33-induced neutrophil infiltration into the peritoneal cavity also showed a time-of-day-dependent variation in wild-type mice, which was absent in ClockÎ19/Î19 mice. Furthermore, IL-33-induced IL-13 and Gob-5 expression in the lung exhibited a time-of-day-dependent variation in wild-type mice. These temporal variations in IL-33-mediated mast cell responses were associated with temporal variations of ST2 expression in mast cells. In addition, CLOCK bound to the promoter region of ST2 and Clock deletion resulted in down-regulation of ST2 expression in mast cells.ConclusionsCLOCK temporally gates mast cell responses to IL-33 via regulation of ST2 expression. Our findings provide novel insights into IL-33/mast cell-associated physiology and pathologies.
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Journal: Allergology International - Volume 66, Issue 3, July 2017, Pages 472-478