TGF- β1 Decreases β2-Agonist-Induced Relaxation in Human Airway Smooth Muscle.

TGF-β1 Decreases β2-Agonist-Induced Relaxation in Human Airway Smooth Muscle. Am J Respir Cell Mol Biol. 2019 Feb 11;: Authors: Ojiaku CA, Chung E, Parikh V, Williams JK, Schwab A, Fuentes AL, Corpuz ML, Lui V, Paek S, Bexiga NM, Narayan S, Nunez FJ, Ahn K, Ostrom RS, An SS, Panettieri RA Abstract Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor beta 1 (TGF-β1), induces HASM cell shortening and airway hyper-responsiveness (AHR). Here we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β2-agonists, a mainstay treatment for AHR in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated isolated HASM cells. This single-cell mechanical hypo-responsiveness to ISO was corroborated by sustained increases in myosin light chain (MLC) phosphorylation. In TGF-β1 treated HASM cells, ISO evoked markedly lower levels of intracellular cAMP. These attenuated cAMP levels were, in turn, restored with pharmacological and siRNA inhibition of PDE4 and Smad3, respectively. Most strikingly, TGF-β1 selectively induced PDE4D gene expression in HASM cells in a Smad2/3-dependent manner. Together these data suggest that TGF-β1 decreases HASM cell β2-agonist relaxation responses by modulating intracellular...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research