首页|Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate cells results in decreased secretion of IL-6

Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate cells results in decreased secretion of IL-6

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AIM:To investigate the mechanism of interleukin (IL)-6 secretion through blocking the IL-17A/IL-17A receptor (IL-17RA) signaling pathway with a short hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro.METHODS:HSCs were derived from the livers of adult male Sprague-Dawley rats.IL-6 expression was evaluated using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay.The phosphorylation activity of p38 mitogen activated protein kinases (MAPK) and extracellular regulated protein kinases (ERK) 1/2 upon induction by IL-17A and suppression by IL-17RA shRNA were examined using Western blotting.RESULTS:IL-6 expression induced by IL-17A was sig-nificantly increased compared to control in HSCs (P ＜0.01 in a dose-dependent manner).Suppression of IL-17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by IL-17A compared to group with only IL-17A treatment (1.44 ± 0.17 vs 4.07 ± 0.43,P ＜ 0.01).IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5 min exposure,and showed the strongest levels of phosphorylation of p38 MAPK and ERK1/2 at 15 min in IL-17A-treated HSCs.IL-6 mRNA expression induced by IL-17A (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups without inhibitors preincubation (1.67 ± 0.24,2.01 ± 0.10 vs 4.08 ±0.59,P ＜ 0.01).Moreover,Lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced IL-6 mRNA expression compared to random shRNA in HSCs (1.44 ±0.17 vs 3.98 4-0.68,P ＜ 0.01).Lentiviral-mediated IL-17RA shRNA 1 inhibited phosphorylation of p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure.CONCLUSION:Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs.Suppression of IL-17RA expression may be a strategy to reduce the inflammatory response induced by IL-17A in the liver.

Interleukin 17AInterleukin 6Hepatic stellate cellsLiver fibrosis

Sheng-Chu Zhang、Yi-Hu Zheng、Pan-Pan Yu、Tan Hooi Min、Fu-Xiang Yu、Chao Ye、Yuan-Kang Xie

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Department of General Surgery,The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China

Stem Cell Center, Lund University, 22184 Lund,Sweden

Department of Infectious Disease, Binjiang Hospital of Hangzhou, Hangzhou 310051, Zhejiang Province, China

2012

10.3748/wjg.v18.i28.3696

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(28)
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