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