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Cigarette smoke and A‐kinase anchoring proteins (AKAPs) in human airway smooth muscle function
Author(s) -
Schmidt Martina,
Oldenburger Anouk,
Poppinga Wilfred,
Roscioni Sara S,
Heijink Irene H,
Timens Wim,
Skroblin Philip,
Klussmann Enno,
Maarsingh Harm
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.864.6
Subject(s) - activator (genetics) , copd , protein kinase a , medicine , phosphodiesterase , proinflammatory cytokine , roflumilast , airway , microbiology and biotechnology , kinase , inflammation , endocrinology , chemistry , biology , enzyme , receptor , anesthesia , biochemistry
COPD is a chronic inflammatory disease mainly caused by cigarette smoke (CS) and characterized by infiltration of (activated) inflammatory cells. Airway smooth muscle (ASM) also contribute to inflammatory cytokine release, smooth muscle contraction, and airway remodeling. Notably, cAMP‐elevating β 2 ‐agonists and phosphodiesterase inhibitors differentially diminish COPD symptoms. Compartmentalization of cAMP by AKAPs could explain distinct cAMP responses. In human ASM, CS‐induced IL‐8 release was decreased by fenoterol, the PKA activator 6‐Bnz‐cAMP, while the Epac activator 8‐pCPT‐2′‐O‐Me‐cAMP showed only slight effects. Addition of PKA‐AKAP interaction inhibitor Ht31 augmented the IL‐8 release. RII overlay, western blots and RT‐qPCR demonstrated expression of AKAP79, AKAP250 and AKAP450. CSE decreased AKAP250, whereas AKAP79 was less affected and AKAP450 even enhanced, indicating disturbation of AKAP functions by CSE. Importantly, similar changes in AKAP expression were found in lung tissues of COPD patients. Our studies provide the first relation between cigarette smoke and the coordination of cAMP signaling by AKAPs. Supported by the Dutch Asthma Foundation and a Rosalind Franklin Fellowship.