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p38 MAP kinase regulates TNFα‐, IL‐1α‐ and PAF‐induced RANTES and GM‐CSF production by human bronchial epithelial cells
Author(s) -
Shigeo Hashimoto,
Ken Matsumoto,
Yasuhiro Gon,
Shuichiro Maruoka,
Kousei Kujime,
S. Hayashi,
Ikuko Takeshita,
Takashi Horie
Publication year - 2000
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.2000.00641.x
Subject(s) - p38 mitogen activated protein kinases , mitogen activated protein kinase , kinase , allergic inflammation , cytokine , platelet activating factor , map kinase kinase kinase , mapk14 , microbiology and biotechnology , biology , protein kinase a , immunology , inflammation
Background RANTES and granulocyte macrophage‐colony stimulating factor (GM‐CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen‐activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM‐CSF production in human bronchial epithelial cells (BECs) has not yet been determined. Objective In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)‐α, interleukin (IL)‐1α and platelet‐activating factor (PAF)‐stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM‐CSF expression in order to clarify the intracellular signal regulating RANTES and GM‐CSF production by human BECs. Results The results showed that TNFα, IL‐1α and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM‐CSF production by TNFα‐, IL‐1α‐ or PAF‐stimulated human BECs. Conclusions These results indicate that p38 MAP kinase plays an important role in TNFα‐, IL‐1α‐ or PAF‐activated signalling pathway which regulates RANTES and GM‐CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway.