Membrane-anchored CD14 is required for LPS-induced TLR4 endocytosis in TLR4/MD-2/CD14 overexpressing CHO cells |
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Authors: | Shuto Tsuyoshi Kato Kosuke Mori Yoko Viriyakosol Suganya Oba Mariko Furuta Takashi Okiyoneda Tsukasa Arima Hidetoshi Suico Mary Ann Kai Hirofumi |
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Affiliation: | Department of Molecular Medicine, Kumamoto University, Kumamoto 862-0973, Japan. |
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Abstract: | Lipopolysaccharide (LPS) induces inflammatory activation through TLR4 (toll-like receptor-4)/MD-2 (myeloid differentiation-2)/CD14 (cluster of differentiation-14) complex. Although optimal LPS signaling is required to activate our innate immune systems against gram-negative bacterium, excessive amount of LPS signaling develops a detrimental inflammatory response in gram-negative bacterial infections. Downregulation of surface TLR4 expression is one of the critical mechanisms that can restrict LPS signaling. Here, we found that membrane-anchored CD14 is required for LPS-induced downregulation of TLR4 and MD-2 in CHO cells. Moreover, pretreatment of the cells with sterol-binding agent filipin reduced LPS-induced TLR4 downregulation, suggesting the involvement of caveolae-mediated endocytosis pathway. Involvement of caveolae in LPS-induced TLR4 endocytosis was further confirmed by immunoprecipitation. Thus, our data indicate that caveolae-dependent endocytosis pathway is involved in LPS-induced TLR4 downregulation and that this is dependent on membrane-anchored CD14 expression. |
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Keywords: | Toll-like receptor 4 Lipopolysaccharide CD14 Caveolae Endocytosis Chinese hamster ovary cells MD-2 |
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