| Summary: | 碩士 === 國立陽明大學 === 傳統醫藥研究所 === 100 === Activation of hepatic stellate cell (HSCs) plays a major role in liver fibrosis. In liver injury, activated HSCs migrate to injured regions in response to chemotactic mediators and then produce collagen to repair the damage. CXCL9 is a chemokine secreted by hepatocytes and sinusoidal endothelial cells. It can bind to HSCs through its receptor CXCR3. Curcumin, a yellow curry pigment from turmeric (Curcuma longa Linn), has been shown to possess anti-inflammatory and antioxidant properties. In this study, we investigated if curcumin can inhibit the activation of HSCs by CXCL9.
A cell line of rat HSC-T6 was stimulated with CXCL9 (100 ng/ml). Cytotoxicity was assessed by the MTT assay. Chemotaxis was evaluated by the wound healing assay. Phosphorylations of Akt and mitogen-activated protein kinases (MAPKs) including ERK1/2, JNK1/2 and p38 were detected using Western blotting. The results revealed that CXCL9 at 100 ng/ml induced cell migration of HSC-T6 cells, and pre-exposure of cells to curcumin (0.25 ~ 2 μM) inhibited the stimulatory effect of CXCL9 in a concentration-dependent manner without causing cytotoxicity. CXCL9 enhanced phosphorylations of Akt and MAPKs at 10 and 15 minutes, respectively. Furthermore, Akt and MAPKs inhibitors, LY294002, PD98059, SP600125 and SB203580, respectively could prevent CXCL9-induced cell migration.
In conclusion, CXCL9 induced migration of HSC-T6 cells in association with Akt and MAPK phosphorylations, and the cell migration induced by CXCL9 was attenuated by curcumin.
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