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Role of early‐ or late‐phase activation of p38 mitogen‐activated protein kinase induced by tumour necrosis factor‐α or 2,4‐dinitrochlorobenzene during maturation of murine dendritic cells
Author(s) -
Iijima Norifumi,
Yanagawa Yoshiki,
Onoé Kazunori
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01746.x
Subject(s) - cd86 , cd80 , p38 mitogen activated protein kinases , mapk/erk pathway , tumor necrosis factor alpha , major histocompatibility complex , microbiology and biotechnology , mitogen activated protein kinase , protein kinase a , chemistry , dendritic cell , immunology , immune system , kinase , cancer research , biology , t cell , cd40 , in vitro , cytotoxic t cell , biochemistry
Summary Dendritic cells (DCs) are maturated by a variety of stimuli. However, the precise mechanisms underlying the maturation of DCs are not fully understood. In the present study, we analysed the effects of tumour necrosis factor‐α (TNF‐α) and 2,4‐dinitrochlorobenzene (DNCB) on phenotypic maturation and p38 mitogen activated protein kinase (MAPK) activity, using a murine DC line. TNF‐α markedly increased the surface expression of major histocompatibility complex (MHC) and costimulatory molecules, CD86 and CD80, on DCs. DNCB more markedly enhanced the surface expression of costimulatory molecules, but showed less stimulatory capability on MHC molecules, compared with TNF‐α. Simultaneous treatment of DCs with TNF‐α and DNCB showed additive enhancement of costimulatory molecule expression. TNF‐α activated p38 MAPK in DCs only at an early time‐point (15 min). In contrast, DNCB activated p38 MAPK at later time‐points (3–6 hr). SB203580, a specific inhibitor of p38 MAPK, partially or markedly inhibited the phenotypic changes of DCs induced by TNF‐α or DNCB, respectively. In addition, N ‐acetyl‐ l ‐cysteine, a reducing supplier, completely inhibited the DNCB‐induced expression of MHC and costimulatory molecules, but not those induced by TNF‐α. These findings demonstrate that TNF‐α and DNCB activate the p38 MAPK pathway at an early and a late phase, respectively, and thereby induce DC maturation through different signal pathways.