Title

β-Adrenergic Receptors Stimulate IL-6 Production in Human Bronchial Smooth Muscle Cells: Enhancement by Non-Raft AC2 But Not Lipid Raft AC6

Document Type

Abstract

Publication Date

2011

Abstract

In human bronchial smooth muscle cells (hBSMC) various isoforms of adenylyl cyclase (AC) are localized to different compartments: AC6 in lipid rafts and caveolae, AC2 outside of rafts. This localization of AC isoforms associates them with different receptors, G proteins and downstream signaling proteins. We hypothesized that specific AC isoforms overexpressed in hBSMC might have differing effects on gene expression. We overexpressed AC2 and AC6 and measured a variety of genes whose expression is influenced by cAMP. Cells were treated with vehicle or the AC activator, forskolin (Fsk). Interleukin 6 (IL-6) mRNA levels were enhanced by Fsk, particularly when AC2 was overexpressed. Fsk-stimulated IL-6 mRNA levels (qRT-PCR) peaked in 1 hr while protein levels (ELISA) peaked at 24 hr. Agonists selective for Gs-coupled GPCR were tested for their ability to stimulate IL-6 in AC2 or AC6 overexpressing cells. Increases in cAMP and IL-6 were observed in response to isoproterenol, PGE2, butaprost and beraprost. AC2, but not AC6, overexpression increased IL-6 production by these agonists. Increasing cAMP levels via Gs/Fsk synergy led to no increase in IL-6 as compared to agonists alone. These data imply that AC2 signaling can lead to IL-6 production by hBSMC but that little correlation exists between cellular cAMP levels and the level of this pro-inflammatory cytokine produced.

Comments

This abstract was originally published in FASEB Journal, volume 25, issue 1 (supplement), in 2011.

Copyright

Federation of American Society of Experimental Biology (FASEB)