IL-10 inhibits cardiac fibroblasts proliferation and phenotype transformation induced by TGF-β1 in rats / 基础医学与临床

ABSTRACT

Objective To examine the effects of IL-10 on cardiac fibroblasts ( CFBs) proliferation and phenotype transformation to myofibroblasts (MyoFbs) induced by transforming growth factor-β1 (TGF-β1);and to investigate the regulating pathways .Methods Cardiac fibroblasts were isolated from cardiac ventricles of neonatal SD rats . The passage 2~4 were used and divided into the following groups for treatment1) control group, 2) IL-10 reac-tion group, 3) TGF-β1 reaction group, and 4) IL-10 plus TGF-β1 reaction group (TGF-β1 treatment followed with IL-10 pretreatment ) .Cells proliferation was assessed by MTT assay and immunocytochemistry staining for prolifera-ting cell nuclear antigen (PCNA);the phenotype transformation into MyoFbs was assessed by immunocytochemistry of α-smooth muscle actin (α-SMA);extracellular signal related kinase ( ERK1/2) and P38 kinase pathways were assessed by western-blot.Results TGF-β1 (10 μg/L) treatment boosted the proliferation and the expression ofα-SMA significantly (P<0.01), while IL-10 (10, 50 or 100 μg/L) plus TGF-β1 co-treatment induced lower cell proliferation and expression of α-SMA than treating with TGF-β1 alone ( P<0.05 ) , with the inhibitory effect of IL-10 being concentration dependent .TGF-β1 could significantly stimulate the ERK 1/2 and P38 kinase phospho-rylation ( P<0.01 ) , however IL-10 (100 μg/L) plus TGF-β1 co-treatment failed to down-regulated the phospho-rylation of ERK1/2 and P38 kinase compared with TGF-β1 alone ( ERK1/2P<0.05;P38P<0.01 ) .Conclu-sions IL-10 can attenuate TGF-β1-induced CFBs proliferation and phenotype transformation to MyoFbs .The in-hibitory effects may explained by a mechanism of inhibiting the activation of ERK 1/2 and P38 kinase .