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Involvement of PKC, p38 MAPK and AP‐2 in IL‐1β‐induced expression of cyclooxygenase‐2 in human pulmonary epithelial cells
Author(s) -
CHEN Ping,
CAI Ying,
YANG ZhiGang,
ZHOU Rui,
ZHANG GuangShen,
DOMANN Frederick,
FANG Xiang
Publication year - 2006
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2006.00779.x
Subject(s) - protein kinase a , p38 mitogen activated protein kinases , a549 cell , mitogen activated protein kinase kinase , microbiology and biotechnology , protein kinase c , ask1 , map kinase kinase kinase , map2k7 , mapk/erk pathway , kinase , c raf , transfection , cyclin dependent kinase 2 , biology , cancer research , cell culture , cell , biochemistry , genetics
Objective: The aim of this study was to identify the signal molecules involved in IL‐1β‐induced expression of cyclooxygenase (COX)‐2 in human pulmonary epithelial (A549) cells. Methods: A549 cells were stimulated with IL‐1β in the presence or absence of H‐7 (a protein kinase C inhibitor), SB203580 (a p38 mitogen‐activated protein kinase inhibitor) and PD098059 (a mitogen‐activated and extracellular regulated kinase kinase (MEK1) inhibitor). The A549 cells were also transfected with adenovirus vector encoding activator protein (AP)‐2α, or a plasmid containing a dominant‐negative gene (AP‐2Δ), in the presence or absence of IL‐1β. Results: IL‐1β induced expression of the COX‐2 mRNA and protein in A549 cells in a time‐ and dose‐dependent manner. SB203580 and H‐7, but not PD098059, inhibited IL‐1β‐induced expression of COX‐2 protein. Overexpression of AP‐2α increased expression of the COX‐2 protein, whereas AP‐2Δ decreased IL‐1β‐induced COX‐2 expression. Conclusion: Protein kinase C, p38 mitogen‐activated protein kinase and transcriptional factor AP‐2α may play important roles in regulating IL‐1β‐induced COX‐2 expression in human pulmonary epithelial cells.