Involvement of mitogen-activated protein kinases and NFkappaB in LPS-induced CD40 expression on human monocytic cells.

Involvement of mitogen-activated protein kinases and NFkappaB in LPS-induced CD40 expression on human monocytic cells. Research Abstract Details 

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Involvement of mitogen-activated protein kinases and NFkappaB in LPS-induced CD40 expression on human monocytic cells. Abstract Text:

CD40 is a costimulatory molecule linking innate and adaptive immune responses to bacterial stimuli, as well as a critical regulator of functions of other costimulatory molecules. The mechanisms regulating lipopolysaccharide (LPS)-induced CD40 expression have not been adequately characterized in human monocytic cells. In this study we used a human monocytic cell line, THP-1, to investigate the possible mechanisms of CD40 expression following LPS exposure. Exposure to LPS resulted in a dose- and time-dependent increase in CD40 expression. Further studies using immunoblotting and pharmacological inhibitors revealed that mitogen-activated protein kinases (MAPKs) and NFkappaB were activated by LPS exposure and involved in LPS-induced CD40 expression. Activation of MAPKs was not responsible for LPS-induced NFkappaB activation. TLR4 was expressed on THP-1 cells and pretreatment of cells with a Toll-like receptor 4 (TLR4) neutralizing antibody (HTA125) significantly blunted LPS-induced MAPK and NFkappaB activation and ensuing CD40 expression. Additional studies with murine macrophages expressing wild type and mutated TLR4 showed that TLR4 was implicated in LPS-induced ERK and NFkappaB activation, and CD40 expression. Moreover, blockage of MAPK and NFkappaB activation inhibited LPS-induced TLR4 expression. In summary, LPS-induced CD40 expression in monocytic cells involves MAPKs and NFkappaB.

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Involvement of mitogen-activated protein kinases and NFkappaB in LPS-induced CD40 expression on human monocytic cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Toxicology and applied pharmacology

VOLUME: 228

Page Numbers: 135-43

Journal Abbreviation: Toxicol. Appl. Pharmacol.

ISSN: 0041-008X

DAY: 14

MONTH: 12

YEAR: 2007

Involvement of mitogen-activated protein kinases and NFkappaB in LPS-induced CD40 expression on human monocytic cells. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Involvement of mitogen-activated protein kinases and NFkappaB in LPS-induced CD40 expression on human monocytic cells.

AFFILIATION: Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA; Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

Country: United States

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MEDLINETA: Toxicol Appl Pharmacol

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