Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

查看全文 作　　者：Mingyong [1,2]Wang;Yue [1]Chen;Yani [1]Zhang;Liyun [1]Zhang;Xiao [1]Lu;Zhengliang [1]Chen

机构地区：[1]Department of Immunology,Southern Medical University,Guangzhou,510515,China;[2]Department of Medical Tests,Xinxiang Medical University,Xinxiang,453003,China

出　　处：《Cellular & Molecular Immunology》索引2011年第8卷第3期,共11页

基　　金：This work was supported by the Natural Science Foundation of China(30972679). 摘　　要：Mannan-binding lectin(MBL)plays a key role in the lectin pathway of complement activation and can influence cytokine expression.Toll-like receptor 4(TLR4)is expressed extensively and has been demonstrated to be involved in lipopolysaccharide(LPS)-induced signaling.We first sought to determine whether MBL exposure could modulate LPS-induced inflammatory cytokine secretion and nuclear factor-kB(NF-kB)activity by using the monocytoid cell line THP-1.We then investigated the possible mechanisms underlying any observed regulatory effect.Using ELISA and reverse transcriptase polymerase chain reaction(RT-PCR)analysis,we found that at both the protein andmRNAlevels,treatment withMBLsuppresses LPS-induced tumor-necrosis factor(TNF)-a and IL-12 production in THP-1 cells.An electrophoretic mobility shift assay and western blot analysis revealed that MBL treatment can inhibit LPS-induced NF-kB DNA binding and translocation in THP-1 cells.While the binding of MBL to THP-1 cells was evident at physiological calcium concentrations,this binding occurred optimally in response to supraphysiological calcium concentrations.This binding can be partly inhibited by treatment with either a soluble form of recombinant TLR4 extracellular domain or anti-TLR4 monoclonal antibody(HTA125).Activation of THP-1 cells by LPS treatment resulted in increased MBL binding.We also observed that MBL could directly bind to the extracellular domain of TLR4 in a dose-dependent manner,and this interaction could attenuate the binding of LPS to cell surfaces.Taken together,these data suggest that MBL may affect cytokine expression through modulation of LPS-/TLR-signaling pathways.These findings suggest that MBL may play an important role in both immune regulation and the signaling pathways involved in cytokine networks. 关键词：CYTOKINES mannan-binding lectin nuclear factor-kB THP-1 cells Toll-like receptor 4

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Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

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