Resolvin D1, resolvin D2 and maresin 1 activate the GSK3β anti-inflammatory axis in TLR4-engaged human monocytes:

Innate Immunity

ZhenGu¹ 

关键词: CREB;    GSK3β;    inflammation;    LPS;    maresin;    resolvin;   

DOI  :  10.1177/1753425916628618

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

Pro-resolving, docosahexaenoic acid-derived mediators have recently emerged as important potential therapeutic agents for the amelioration of complications arising from inflammation, such as vascular disease, asthma, acute lung injury and colitis. While resolvin D1 (RVD1), resolvin D2 (RVD2) and maresin 1 (MaR1) are established pro-resolvins, their mechanisms of action remain unclear. Here we show that, in LPS-stimulated primary human monocytes, RVD1, RVD2 and MaR1 each suppress the release of pro-inflammatory cytokines (TNF, IL-1β, IL-8) and the innate/adaptive bridging cytokine, IL-12 p40, while simultaneously augmenting the production of the anti-inflammatory cytokine, IL-10. Such resolving activity is accompanied by the increased phosphorylation (enhanced anti-inflammatory state) of glycogen synthase kinase 3β (GSK3β) along with increased phosphorylation (activation) of Akt, SGK1 and CREB but not MAPK-related molecules. Gain and loss of function experiments confirm a key role for GSK3β and CREB in the...

【 授权许可】

CC BY