p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase regulate interleukin-8 and RANTES production in hyperosmolarity stimulated human bronchial epithelial cells.
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-NH2-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.


CONCLUSIONS
These results indicate that p38 MAPK and the JNK pathway regulate hyperosmolarity induced IL-8 and RANTES production by BEC.
Furuichi
Sachiko
S
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hashimoto
Shu
S
Gon
Yasuhiro
Y
Matsumoto
Ken
K
Horie
Takashi
T
D000704:Analysis of Variance; D001250:Asthma, Exercise-Induced / Q000503:physiopathology; D001980:Bronchi / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D009994:Osmolar Concentration; D048051:p38 Mitogen-Activated Protein Kinases
D018946:Chemokine CCL5; D016209:Interleukin-8; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases