文章基本信息

标题：Hyporesponsiveness to the anti-inflammatory action of interleukin-10 in type 2 diabetes
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作者：Julianne C. Barry ; Soroush Shakibakho ; Cody Durrer 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
期号：1
DOI：10.1038/srep21244
语种：English
出版社：Springer Nature
摘要：Chronic low-grade inflammation contributes to the pathology and complications of type 2 diabetes (T2D). Interleukin-10 (IL10), an anti-inflammatory cytokine, is suggested to play a protective role in T2D. However, the impact of T2D on IL10 function has not been previously assessed. We examined the ability of IL10 to inhibit inflammation in human T2D immune cells and explored underlying mechanisms using macrophage models. IL10 was less effective at inhibiting tumour necrosis factor (TNF)-α secretion in T2D whole blood cultures, which was not explained by altered IL10 receptor surface expression. These findings were observed in macrophages exposed to high glucose, which demonstrated similar IL10 resistance or hyporesponsiveness. These findings were also not explained by changes in IL10 receptor protein or other downstream signaling proteins. High glucose was also shown to impair the ability of IL10 to activate STAT3, a downstream signaling protein of IL10. Treatment with the SHIP1 agonist, AQX-MN100, reversed IL10 hyporesponsiveness in macrophages cultured in high glucose and showed equal effectiveness at different glucose conditions. This data supports the idea that IL10 hyporesponsiveness may contribute to chronic inflammation in T2D. These novel findings suggest that strategies aimed to overcome IL10 hyporesponsiveness may hold therapeutic potential for reducing inflammation in T2D.