Paeoniflorin inhibits activation of raw 264.7 macrophages induced by high glucose via JAK2/STAT3 signaling pathway / 中国药理学通报

ABSTRACT

Aim To investigate whether paeoniflorin ( PF) inhibits the activation of RAW 264. 7 macropha-ges induced by high glucose (HG) via JAK2/STAT3 signaling pathway. Methods RAW264. 7 macrophages were cultured in vitro. HG was used as the stimulator. PF and JAK2/STAT3 gene silencing interfered with macrophage activation. All cells were divided into nine groups; LG, HG, HG + PF, LG + JAK2 siRNA, JAK2 siRNA + HG, JAK2 siRNA + HG + PF, LG + STAT3 siRNA,STAT3 siRNA + HG,STAT3 siRNA + HG + PF. Macrophage proliferation, chemotaxis, expression and secretion of inflammatory cytokines, J A K2 and STAT3 protein expression and the phosphorylation levels were detected respectively. Results Compared with LG group,in HG group,the macrophages' chcmo- taclic function significantly increased {P <0. 05) ,the mRNA expression of iNOS,TNF-a, IL-lp and MCP-1 and the secretion of inflammatory cytokines (TNF-a, IL-IP,MCP-1) in cell culture medium were markedly elevated ( P < 0. 05 , P < 0. 01 ) , and the phosphorylation of JAK2 and STAT3 protein significantly increased ( P < 0. 05 ). JAK2 and STAT3 gene silencing could suppress the HG-induced the mRNA expression of iN- OS,TNF-a, 1L-IP and MCP-1 and the secretion inflammatory cytokines in cell culture medium as well as the phosphorylation of JAK2 and STA'13 protein ( P < 0. 05,/' <0. 01 ). PF could significantly inhibit HG-induced macrophage chemokine and migration,inflammatory cytokine production and secretion, and JAK2, STAT3 protein phosphorylation (/'<0. 01). Conclusion HG can stimulate macrophage activation by inducing JAK2/STAT3 signaling pathway,and PF inhibits the activation of Raw 264. 7 macrophages induced by high glucose via JAK2/STAT3 pathway suppression.