Non-raft adenylyl cyclase 2 defines a cAMP signaling compartment that selectively regulates IL-6 expression in airway smooth muscle cells: differential regulation of gene expression by AC isoforms.

Naunyn-Schmiedeberg's Archives of Pharmacology
Amy S BogardRennolds S Ostrom

Abstract

Adenylyl cyclase (AC) isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions. Most cell types express multiple AC isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses in human bronchial smooth muscle cells (BSMC). Overexpression of AC2, AC3, or AC6 had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes. These data show that different AC isoforms can differentially regulate gene expression. Most notable, overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production by BSMC was induced by Fsk and select G protein-coupled receptor (GPCR) agonists, though IL-6 levels did not directly correlate with global cAMP levels. Treatment with PKA selective 6-Bnz-cAMP or Epac selective 8-CPT-2Me-cAMP cAMP analogs revealed a predominant role for PKA in cAMP-mediated induction of IL-6. IL-6 promoter mutations demonstrated that AP-1 and CRE transcription sites were required for Fsk to stimulate IL-6 expression. Our present study defines an AC2 cAMP signaling compartment that specifically regulates IL-6 expression in B...Continue Reading

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Citations

Jun 13, 2017·British Journal of Pharmacology·Shailesh R AgarwalRobert D Harvey
May 10, 2019·The Journal of Pharmacology and Experimental Therapeutics·Shailesh R AgarwalRobert D Harvey
Dec 9, 2017·Molecular Pharmacology·Timothy B JohnstoneRennolds S Ostrom
Dec 21, 2017·American Journal of Respiratory Cell and Molecular Biology·Timothy B JohnstoneRennolds S Ostrom
Apr 16, 2019·Genetics and Molecular Biology·Thiago CorrêaMariluce Riegel
Nov 8, 2020·The Journal of Pharmacology and Experimental Therapeutics·Radhika JoshiMark A Giembycz
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Chenlu LiHaijia Yu

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