Korean J Otolaryngol-Head Neck Surg.  2002 Oct;45(10):957-962.

IL-1beta-Mediated Cyclooxygenase-2 Expression through Activation of PKC-MEK / ERK in Human Airway Epithelial Cells

• Kim YD
• Song SY
• Baek SH
• Cho GS
• Woo HJ
• Yoon SK

Abstract

BACKGROUND AND OBJECTIVES: Cyclooxygenase-2 (COX-2) plays an important role in the biosynthesis of prostaglandin, which is an important inflammatory mediator in human airway inflammatory disease. We observed that interleukin-1beta(IL-1beta) induces COX-2 gene expression and protein production in NCI-H292 cells in the previous experiment and designed this study to investigate the signal transduction pathway of the IL-1beta-mediated COX-2 expression in human airway epithelial cells. MATERIALS AND METHOD: In the cultured human airway NCI-H292 epithelial cells, the IL-1beta-mediated COX-2 gene and protein expression were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. To identify the signal transduction pathway of the IL-1beta-mediated COX-2 expression, we used specific inhibitors.
RESULTS
PD98059, MEK/ERK inhibitor suppressed IL-1beta-mediated COX-2 gene and protein expression, but SB203580, p38 inhibitor did not suppress it. Ro31-8220, PKC inhibitor attenuated IL-1beta-mediated COX-2 gene and protein expression. Ro31-8220 suppressed ERK phosphorylation, but did not inhibit phosphorylation of p38 and JNK. PKC were involved at upstream of ERK in the IL-1beta-mediated COX-2 expression. PI3K inhibitor, LY294002 and tyrosine kinase inhibitor, genistein did not suppress COX-2 expression.
CONCLUSION
IL-1beta-induced COX-2 gene and protein expression is up-regulated through activation of PKC-MEK/ERK cascade in human airway NCI-H292 epithelial cells.

Keyword

Interleukin-1beta; Cyclooxygenase-2; Protein Kinase C; MEK/ERK

MeSH Terms

Blotting, Western
Cyclooxygenase 2*
Epithelial Cells*
Gene Expression
Genistein
Humans*
Interleukin-1beta
Phosphorylation
Protein Kinase C
Protein-Tyrosine Kinases
Signal Transduction
Cyclooxygenase 2
Genistein
Interleukin-1beta
Protein Kinase C
Protein-Tyrosine Kinases