Recombinant HBsAg inhibits LPS-induced COX-2 expression and IL-18 production by interfering with the NFκB pathway in a human monocytic cell line, THP-1
Recombinant HBsAg inhibits LPS-induced COX-2 expression and IL-18 production by interfering with the NFκB pathway in a human monocytic cell line, THP-1
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DOI：
10.1016/j.jhep.2005.02.033
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发表时间：
2005-09-01
影响因子：
25.7
通讯作者：
Hada, T
中科院分区：
文献类型：
--
作者：
Cheng, JD;Imanishi, H;Hada, T
背景/目标：B型肝炎病毒抑制人免疫系统，HBsAg抑制人巨噬细胞中LPS诱导的细胞因子，但涉及的机制仍不清楚。考克斯-2及其产物PGE 2在B型肝炎中起作用，并且IL-18也已被证明在体内抑制HBV感染。我们研究了rHBsAg是否影响LPS诱导考克斯-2和IL-18的表达，如果是，那么哪些信号通路参与了人单核细胞系THP-1的表达。方法：采用细胞培养，Western blotting检测考克斯-2、ERK和IKB-α，免疫荧光检测HBsAg和NF κ B B蛋白，ELISA检测PGE 2、IL-18和IL-12。rHBsAg通过阻断ERK和NF κ B通路，以时间和剂量依赖性方式抑制LPS诱导的考克斯-2表达。LPS诱导的IL-18产生也被rHBsAg下调，主要是通过干扰NF κ B途径。PGE 2可逆转rHBsAg对LPS诱导的IL-18产生的抑制作用。结论：rHBsAg具有抑制考克斯-2的作用，提示B病毒可能通过抑制IL-18和IL-12的产生来调节IFN-γ的产生。(c)2005年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Hepatitis B virus suppresses the human immune-system and HBsAg inhibits the induction of cytokines by LPS in human macrophages, but the mechanisms involved remain unclear. COX-2 and its product, PGE2, play a role in hepatits B and IL-18 has also been shown to inhibit HBV infection in vivo. We investigated whether rHBsAg affects induction of COX-2 and IL-18 by LPS and, if so, which signal pathways are involved in a human monocytic cell line, THP-1.Methods: Cell culture, Western blotting for COX-2, ERK and IKB-alpha, immunofluorescence for HBsAg and NF kappa B protein and ELISA for PGE2, IL-18 and IL-12 were performed.Results: rHBsAg inhibits LPS-induced COX-2 expression in a time- and dose-dependent manner by blocking the ERK and NF kappa B pathways. LPS-induced IL-18 production was also down-regulated by rHBsAg by interfering mainly with the NFKB pathway. PGE2 reversed the inhibition of LPS-induced IL-18 production by rHBsAg. rHBsAg was also found to inhibit the induction of IL-12 by LPS in THP-1 cells.Conclusions: These results showed a novel anti-inflammatory property of rHBsAg which involves inhibition of COX-2 and suggested that hepatits B virus may regulate IFN-gamma production by inhibiting IL-18 and IL-12 production. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.