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p38 Mitogen‐activated protein kinase and c‐Jun‐NH 2 ‐terminal kinase regulate interleukin‐8 and RANTES production in hyperosmolarity stimulated human bronchial epithelial cells
Author(s) -
FURUICHI Sachiko,
HASHIMOTO Shu,
GON Yasuhiro,
MATSUMOTO Ken,
HORIE Takashi
Publication year - 2002
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1046/j.1440-1843.2002.00401.x
Subject(s) - p38 mitogen activated protein kinases , mapk/erk pathway , kinase , mitogen activated protein kinase , microbiology and biotechnology , phosphorylation , protein kinase a , chemistry , biology
Objective: We have previously shown that p38 mitogen‐activated protein kinase (MAPK) regulates, at least in part, hyperosmolarity induced interleukin (IL)‐8 expression in human bronchial epithelial cells (BEC). In the previous study, hyperosmolarity also activated c‐Jun‐NH 2 ‐terminal kinase (JNK); however, the role of the JNK signalling pathway has not been determined. In the present study, we examined the role of the JNK signalling pathway in hyperosmolarity induced IL‐8 and RANTES production by BEC using the novel inhibitor of the JNK signalling pathway CEP 11004 in order to clarify these issues. Methods: Bronchial epithelial cells that had been pre‐incubated with SB 203580, CEP 11004 or a combination of these were exposed to a hyperosmolar medium and then the p38 MAPK and JNK phosphorylation activity in these cells and IL‐8 and RANTES concentrations in the culture supernatants were determined. Results: The results showed that: (i) hyperosmolarity induced the threonine and tyrosine phosphorylation of p38 MAPK and JNK; (ii) SB 203580, as the specific inhibitor of p38 MAPK activity, and CEP 11004 attenuated hyperosmolarity induced p38 MAPK and JNK activity, respectively; (iii) SB 203580 and CEP 11004, but not PD 98059, partially attenuated IL‐8 and RANTES production; and (iv) a combination of SB 203580 and CEP 11004 attenuated IL‐8 and RANTES production in an additive fashion. Conclusion: These results indicate that p38 MAPK and the JNK pathway regulate hyperosmolarity induced IL‐8 and RANTES production by BEC.