Exogenous IL-19 mediates downregulation of TGF-β through Erk and p38 pathway to inhibit epidural fibrosis

摘要

OBJECTIVE: To evaluate the effect of interleukin-19 (IL-19) treatment on epidural fibrosis and its mechanism of action with transforming growth factor β (TGF-β). MATERIALS AND METHODS: Initially, IL-19 (10, 20, 50 and 100 ng/L) was used to pretreat rat fibroblasts. TGF-β (10 μg/L) was then applied to activate fibroblasts. The protein expression levels of TGF-β receptor, extracellular-signal-regulated kinase (Erk) and p-38 were measured by Western blotting. In addition, we performed laminectomy at T10 vertebral plate in rats, followed by injection of IL-19 in caudal vein one week after injury. Furthermore, IL-19, TGF-β and fibrosis indexes were measured by quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blotting at 7 and 28 days after injury, respectively. RESULTS: Concentration-dependent IL-19 significantly down-regulated TGF-β receptor expression and inhibited phosphorylated Erk (p-Erk) and phosphorylated p38 (p-p38). In vivo, IL-19 reduced the expressions of TGF-β and connective tissue growth factor (CTGF) at 7 days. Furthermore, IL-19 significantly suppressed extracellular matrix productions formation, including α smooth muscle actin (α-SMA) and collagen-1 (COL-1), and fibronectin at 28 days. CONCLUSIONS: IL-19 inhibited TGF-β expression via Erk and p38 pathway. Moreover, it decreased CTGF expression to suppress α-SMA, COL-1 and fibronectin in scar tissues, thereby preventing spinal cord from compression of scar tissues.