Over-expression of a RhoA-specific guanine nucleotide exchange factor, p190RhoGEF, in mouse dendritic cells negatively regulates cellular responses to bacterial lipopolysaccharide

• Published in: Molecules and cells 2012, 34(2), , pp.159-164
• Main Authors: Seul, H.J., Ewha Womans University, Seoul, Republic of Korea, Ahn, Y.R., Ewha Womans University, Seoul, Republic of Korea, Song, H.M., Ewha Womans University, Seoul, Republic of Korea, Ha, Y.J., Ewha Womans University, Seoul, Republic of Korea, Lee, J.R., Ewha Womans University, Seoul, Republic of Korea
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cell Biology; Cell Differentiation - drug effects; Cells, Cultured; dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Gene Expression; GTPase-Activating Proteins - biosynthesis; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - immunology; GTPase-Activating Proteins - metabolism; Immunohistochemistry; Life Sciences; LIPOPOLISACARIDOS; LIPOPOLYSACCHARIDE; LIPOPOLYSACCHARIDES; Lipopolysaccharides - immunology; Lipopolysaccharides - pharmacology; Mice; Mice, Transgenic; p190RhoGEF; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Repressor Proteins - immunology; Repressor Proteins - metabolism; Research Article; rhoA GTP-Binding Protein - immunology; rhoA GTP-Binding Protein - metabolism; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-012-0055-9

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.