Involvement of PKC, p38 MAPK and AP-2 in IL-1 beta-induced expression of cyclooxygenase-2 in human pulmonary epithelial cells

Objective: The aim of this study was to identify the signal molecules involved in IL-1 beta-induced expression of cyclooxygenase (COX)-2 in human pulmonary epithelial (A549) cells. Methods: A549 cells were stimulated with IL-1 beta 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)-2 alpha, or a plasmid containing a dominant-negative gene (AP-2 Delta), in the presence or absence of IL-1 beta. Results: IL-1 beta 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-1 beta-induced expression of COX-2 protein. Overexpression of AP-2 alpha increased expression of the COX-2 protein, whereas AP-2 Delta decreased IL-1 beta-induced COX-2 expression. Conclusion: Protein kinase C, p38 mitogen-activated protein kinase and transcriptional factor AP-2 alpha. may play important roles in regulating IL-1 beta-induced COX-2 expression in human pulmonary epithelial cells.