title: Over-expression of a RhoA-specific guanine nucleotide exchange factor, p190RhoGEF, in mouse dendritic cells negatively regulates cellular responses to bacterial lipopolysaccharide.
abstract: We studied the role of a RhoA-specific guanine nucleotide exchange factor (p190RhoGEF) in dendritic cells (DCs), using transgenic (TG) mice that over-express a full gene of p190RhoGEF under the control of an invariant chain promoter. TG mice lacked localization of activated DCs to the T cell zone in the spleen and had reduced serum levels of IL-6 in response to lipopolysaccharide (LPS) injection. DCs from these mice also showed reduced surface expression of CD86, CD40, and CD205, but not MHCII, as well as a reduced capability to uptake antigen. Moreover, chemokine-driven migration and secretion of IL-6, but not of IL-12, were impaired after LPS-stimulation of TG DCs. Collectively, these results suggest that over-expressing p190RhoGEF negatively regulates conventional DC function in response to bacterial LPS infection.
authors: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea.
authors: Hee Jung
authors: HJ
authors: Seul
authors: Yu Ri
authors: YR
authors: Ahn
authors: Hyeon Myeong
authors: HM
authors: Song
authors: Yun Jung
authors: YJ
authors: Ha
authors: Jong Ran
authors: JR
authors: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000276:immunology / Q000378:metabolism
chemical_list: C513041:Arhgap35 protein, mouse; D020690:GTPase-Activating Proteins; D008070:Lipopolysaccharides; D012097:Repressor Proteins; D020742:rhoA GTP-Binding Protein