Activation of extracellular signal-related kinase by TNF-α controls the maturation and function of murine dendritic cells

Abstract

Functional roles of extracellular signal-related kinase (ERK)activation in dendritic-cell (DC) maturation have been unclear. In thepresent study, we investigated the ERK pathway in tumor necrosis factor(TNF)-α-induced maturation of murine spleen-derived DC. TNF-αincreased surface expressions of major histocompatibility(MHC) and costimulatory molecules on DC in a dose-dependentmanner. High (40 ng/ml) and low (0.4 ng/ml) concentrations of TNF-αmarkedly enhanced ERK1/2 activation in DC, and this activation wasblocked completely by PD98059, a selective inhibitor of the ERKpathway. When DC were treated with TNF-α at a low but not a highconcentration, PD98059 notably enhanced surface expressions of the MHCand costimulatory molecules and allostimulatory capability of the DC. Interleukin (IL)-12 production was enhanced significantly by PD98059 in DC treated with low or high concentration of TNF-α. These findingssuggest that TNF-α-induced ERK activation negatively controlsmaturation and IL-12 production in murine DC.