Involvement of PKC, p38 MAPK and AP-2 in IL-1beta-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-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.


CONCLUSIONS
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.
Chen
Ping
P
Department of Respiratory Medicine, The Second Affilitated Hospital, Central-South University, Xiangya Medical School, Changsha, Hunan, China. chenping101@hotmaill.com
Cai
Ying
Y
Yang
Zhi-Gang
ZG
Zhou
Rui
R
Zhang
Guang-Shen
GS
Domann
Frederick
F
Fang
Xiang
X
D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D011493:Protein Kinase C / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000201:enzymology*; D015398:Signal Transduction; D050656:Transcription Factor AP-2 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D007375:Interleukin-1; D050656:Transcription Factor AP-2; D051546:Cyclooxygenase 2; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases