title: Eps8 protein facilitates phagocytosis by increasing TLR4-MyD88 protein interaction in lipopolysaccharide-stimulated macrophages.
abstract: Toll-like receptors (TLRs) are crucial in macrophage phagocytosis, which is pivotal in host innate immune response. However, the detailed mechanism is not fully defined. Here, we demonstrated that the induction of Src and Eps8 in LPS-treated macrophages was TLR4- and MyD88-dependent, and their attenuation reduced LPS-promoted phagocytosis. Confocal microscopy indicated the colocalization of Eps8 and TLR4 in the cytosol and at the phagosome. Consistently, both Eps8 and TLR4 were present in the same immunocomplex regardless of LPS stimulation. Inhibition of this complex formation by eps8 siRNA or overexpression of pleckstrin homology domain-truncated Eps8 (i.e. 261-p97(Eps8)) decreased LPS-induced TLR4-MyD88 interaction and the following activation of Src, focal adhesion kinase, and p38 MAPK. Importantly, attenuation of Eps8 impaired the bacterium-killing ability of macrophages. Thus, Eps8 is a key regulator of the LPS-stimulated TLR4-MyD88 interaction and contributes to macrophage phagocytosis.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Yen-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Miao Ying
authors.initials: MY
authors.lastname: Chang
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Chen
authors.forename: Ming-Shiou
authors.initials: MS
authors.lastname: Jan
authors.forename: Ming-Chei
authors.initials: MC
authors.lastname: Maa
authors.forename: Tzeng-Horng
authors.initials: TH
authors.lastname: Leu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C083430:Eps8 protein, mouse; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4