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 treatment: 1) control group, 2) IL-10 reaction 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 proliferating cell nuclear antigen (PCNA); the phenotype transformation into MyoFbs was assessed by immunocytochemistry of α-smooth muscle actin (α-SMA); and extracellular signal related kinase (ERK1/2) and p38 kinase pathways were assessed by western-blot. Results TGF-β1(10μg/L) treatment boosted the proliferation and the expression of α-SMA significantly (P＜0.01), while IL-10 (10, 50 or 100μg/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 ERK1/2 and p38 kinase phosphorylation (P＜0.01), however IL-10 (100μg/L) plus TGF-β1 co-treatment could down-regulated the phosphorylation of ERK1/2 and p38 kinase compared with TGF-β1 alone (ERK1/2：P＜0.05；p38：P＜0.01). Conclusions IL-10 can attenuate TGF-β1-induced CFBs proliferation and phenotype transformation to MyoFbs. The inhibitory effects could involve a mechanism of inhibiting the activation of ERK1/2 and p38 kinase.

Key words: interleukin-10, cardiac fibroblasts, transforming growth factor-β1, extracellular signal related kinase, p38 kinase