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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / drug effects
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Cells, Cultured
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Dendritic Cells / cytology
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Dendritic Cells / drug effects*
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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GTPase-Activating Proteins / biosynthesis*
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GTPase-Activating Proteins / genetics
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GTPase-Activating Proteins / immunology
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GTPase-Activating Proteins / metabolism
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Gene Expression
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Immunohistochemistry
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Lipopolysaccharides / immunology
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Lipopolysaccharides / pharmacology*
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Mice
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Mice, Transgenic
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Repressor Proteins / biosynthesis*
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Repressor Proteins / genetics
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Repressor Proteins / immunology
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Repressor Proteins / metabolism
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rhoA GTP-Binding Protein / immunology
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rhoA GTP-Binding Protein / metabolism
Substances
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Arhgap35 protein, mouse
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GTPase-Activating Proteins
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Lipopolysaccharides
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Repressor Proteins
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rhoA GTP-Binding Protein