IL-10 Inhibits Inflammation and Attenuates Left Ventricular Remodeling After Myocardial Infarction via Activation of STAT3 and Suppression of HuR

Abstract

Abstract-Persistent inflammatory response has adverse effects on left ventricular (LV) function and remodeling following acute myocardial infarction. We hypothesized that suppression of inflammation with interleukin (IL)-10 treatment attenuates LV dysfunction and remodeling after acute myocardial infarction. After the induction of acute myocardial infarction, mice were treated with either saline or recombinant IL-10, and inflammatory response and LV functional and structural remodeling changes were evaluated. IL-10 significantly suppressed infiltration of inflammatory cells and expression of proinflammatory cytokines in the myocardium. These changes were associated with IL-10 -mediated inhibition of p38 mitogen-activated protein kinase activation and repression of the cytokine mRNA-stabilizing protein HuR. IL-10 treatment significantly improved LV functions, reduced infarct size, and attenuated infarct wall thinning. Myocardial infarction-induced increase in matrix metalloproteinase (MMP)-9 expression and activity was associated with increased fibrosis, whereas IL-10 treatment reduced both MMP-9 activity and fibrosis. Small interfering RNA knockdown of HuR mimicked IL-10 -mediated reduction in MMP-9 expression and activity in NIH3T3 cells. Moreover, IL-10 treatment significantly increased capillary density in the infarcted myocardium which was associated with enhanced STAT3 phosphorylation. Taken together, our studies demonstrate that IL-10 suppresses inflammatory response and contributes to improved LV function and remodeling by inhibiting fibrosis via suppression of HuR/MMP-9 and by enhancing capillary density through activation of STAT3. (Circ Res. 2009;104:e9-e18.)

Jian carp ( Cyprinus carpio var. Jian) intestinal immune responses, antioxidant status and tight junction protein mRNA expression are modulated via Nrf2 and PKC in response to dietary arginine deficiency

“…Study showed that upregulation of the pro-inflammatory cytokines IL-1 and TNF-a were involved in the inflammatory response [41]. Meanwhile, upregulation of the gene expression of anti-inflammatory cytokines IL-10 and TGF-b could attenuate the inflammatory response [42]. In the present study, fish fed the arginine-deficient diet significantly increased the gene expression of IL-1b in Jian carp intestine.…”

Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model

“…Studies in other organs, including lung, heart, pancreas and liver, also showed IL-10 could suppress inflammatory response and thereby inhibit matrix remodeling and fibrosis process, even if fibrosis had developed. [31][32][33][34][35][36][37] Here, we provide direct evidence supporting the role of IL-10 in renal fibrosis by demonstrating that knockout of IL-10 leads to more severe inflammatory response and renal injury and fibrosis in the UUO model. In addition, we found that knockout of IL-10 enhanced activation of TGF-b/Smad3 and NF-kB pathways at days 7 and 14 after UUO, which are known to have central roles in the initiation and progression of renal inflammation and fibrosis through inducing a wide array of genes encoding pro-inflammatory cytokines, adhesion molecules, and chemokines in human and experimental models of kidney diseases.…”

Dietary riboflavin deficiency decreases immunity and antioxidant capacity, and changes tight junction proteins and related signaling molecules mRNA expression in the gills of young grass carp (Ctenopharyngodon idella)

“…It was reported that the up-regulation of pro-inflammatory cytokines, such as IL-8, TNF-a, IFN-g and IL-1b [61,62], and the downregulation of anti-inflammatory cytokines, such as IL-10 and TGFb [63,64] initiated inflammatory process. In this study, compared with optimal riboflavin supplementation, riboflavin deficiency increased pro-inflammatory cytokines IL-1b, IL-8, IFN-g2 and TNFa mRNA levels, and decreased anti-inflammatory cytokines IL-10 and TGF-b1 mRNA levels in the gills of young grass carp (Fig.…”