Regulatory features of interleukin-1beta-mediated prostaglandin E2 synthesis in airway smooth muscle.

Authors

• Rodolfo M Pascual
• Elizabeth M Carr
• Michael C Seeds
• Manhong Guo
• Reynold A Panettieri
• Stephen P Peters
• Raymond B Penn

Publication/Presentation Date

3-1-2006

Abstract

Exposure of airway smooth muscle (ASM) cells to the cytokine IL-1beta results in an induction of PGE2 synthesis that affects numerous cell functions. Current dogma posits induction of COX-2 protein as the critical, obligatory event in cytokine-induced PGE2 production, although PGE2 induction can be inhibited without a concomitant inhibition of COX-2. To explore other putative regulatory features we examined the role of phospholipase A2 (PLA2) and PGE synthase (PGES) enzymes in IL-1beta-induced PGE2 production. Treatment of human ASM cultures with IL-1beta caused a time-dependent induction of both cytosolic PLA2 (cPLA2) and microsomal PGES (mPGES) similar to that observed for COX-2. Regulation of COX-2 and mPGES induction was similar, being significantly reduced by inhibition of p42/p44 or p38, whereas cPLA2 induction was only minimally reduced by inhibition of p38 or PKC. COX-2 and mPGES induction was subject to feed-forward regulation by PKA, whereas cPLA2 induction was not. SB-202474, an SB-203580 analog lacking the ability to inhibit p38 but capable of inhibiting IL-1beta-induced PGE2 production, was effective in inhibiting mPGES but not COX-2 or cPLA2 induction. These data suggest that although COX-2, cPLA2, and mPGES are all induced by IL-beta in human ASM cells, regulatory features of cPLA2 are dissociated, whereas those of COX-2 and mPGES are primarily associated, with regulation of PGE2 production. mPGES induction and, possibly, cPLA2 induction appear to cooperate with COX-2 to determine IL-1beta-mediated PGE2 production in human ASM cells.

Volume

290

Issue

3

First Page

501

Last Page

508

ISSN

1040-0605

Published In/Presented At

Pascual, R. M., Carr, E. M., Seeds, M. C., Guo, M., Panettieri, R. A., Jr, Peters, S. P., & Penn, R. B. (2006). Regulatory features of interleukin-1beta-mediated prostaglandin E2 synthesis in airway smooth muscle. American journal of physiology. Lung cellular and molecular physiology, 290(3), L501–L508. https://doi.org/10.1152/ajplung.00420.2005

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

16299051

Department(s)

Administration and Leadership

Document Type

Article