Anti-inflammatory role of the cAMP effectors Epac and PKA: implications in chronic obstructive pulmonary disease.

PloS One
Anouk OldenburgerMartina Schmidt

Abstract

Cigarette smoke-induced release of pro-inflammatory cytokines including interleukin-8 (IL-8) from inflammatory as well as structural cells in the airways, including airway smooth muscle (ASM) cells, may contribute to the development of chronic obstructive pulmonary disease (COPD). Despite the wide use of pharmacological treatment aimed at increasing intracellular levels of the endogenous suppressor cyclic AMP (cAMP), little is known about its exact mechanism of action. We report here that next to the β(2)-agonist fenoterol, direct and specific activation of either exchange protein directly activated by cAMP (Epac) or protein kinase A (PKA) reduced cigarette smoke extract (CSE)-induced IL-8 mRNA expression and protein release by human ASM cells. CSE-induced IκBα-degradation and p65 nuclear translocation, processes that were primarily reversed by Epac activation. Further, CSE increased extracellular signal-regulated kinase (ERK) phosphorylation, which was selectively reduced by PKA activation. CSE decreased Epac1 expression, but did not affect Epac2 and PKA expression. Importantly, Epac1 expression was also reduced in lung tissue from COPD patients. In conclusion, Epac and PKA decrease CSE-induced IL-8 release by human ASM cells ...Continue Reading

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Citations

Jul 6, 2014·Naunyn-Schmiedeberg's Archives of Pharmacology·Anouk OldenburgerMartina Schmidt
Jan 16, 2013·Hypertension·Patrick Crosswhite, Zhongjie Sun
Apr 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Seiko Susuki-MiyataJian-Dong Li
Oct 24, 2012·Pharmacology & Therapeutics·Bart G J DekkersMartina Schmidt
Apr 1, 2015·British Journal of Pharmacology·Eva WexPhilippe Devillier
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Mar 15, 2018·Physiological Reviews·William G Robichaux, Xiaodong Cheng
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Jun 19, 2013·Pharmacological Reviews·Utako YokoyamaYoshihiro Ishikawa
Feb 1, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·Wilfred J PoppingaMartina Schmidt
Sep 6, 2019·American Journal of Respiratory Cell and Molecular Biology·Dinesh DevadossHitendra S Chand
Aug 12, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anouk OldenburgerMartina Schmidt
Oct 23, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nilesh Sudhakar AmbhoreVenkatachalem Sathish
May 19, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Klaus AktoriesThomas Wieland
Jan 24, 2014·American Journal of Physiology. Cell Physiology·Anouk OldenburgerMartina Schmidt
Nov 11, 2018·International Journal of Molecular Sciences·Byung-Cheol LeeJian-Dong Li
Jul 1, 2020·Biochemical Society Transactions·Isabella Cattani-CavalieriMartina Schmidt
Apr 17, 2021·Biochemical Society Transactions·Jonathan K H LiMark R Johnson

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Methods Mentioned

BETA
biopsies
nuclear translocation
transfection
ELISA
protein assay
electrophoresis
PCR

Software Mentioned

Promega
ColorView

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