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(Journal of Leukocyte Biology. 2002;71:125-132.)
© 2002 by Society for Leukocyte Biology

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

Yoshiki Yanagawa, Norifumi Iijima, Kazuya Iwabuchi and Kazunori Onoé

Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan

Correspondence: Dr. K. Onoé, Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815 Japan. E-mail: kazunori{at}imm.hokudai.ac.jp

Functional roles of extracellular signal-related kinase (ERK) activation in dendritic-cell (DC) maturation have been unclear. In the present study, we investigated the ERK pathway in tumor necrosis factor (TNF)-{alpha}-induced maturation of murine spleen-derived DC. TNF-{alpha} increased surface expressions of major histocompatibility (MHC) and costimulatory molecules on DC in a dose-dependent manner. High (40 ng/ml) and low (0.4 ng/ml) concentrations of TNF-{alpha} markedly enhanced ERK1/2 activation in DC, and this activation was blocked completely by PD98059, a selective inhibitor of the ERK pathway. When DC were treated with TNF-{alpha} at a low but not a high concentration, PD98059 notably enhanced surface expressions of the MHC and 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-{alpha}. These findings suggest that TNF-{alpha}-induced ERK activation negatively controls maturation and IL-12 production in murine DC.

Key Words: MAPK • PD98059 • IL-12 • APC




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