The purpose of this study was to investigate whether growth factors produced by activated human lung mast cells (HLMCs) impair β -adrenoceptor (β -AR) function in human airway smooth muscle (ASM) cells. Protein array analysis confirmed the presence of various growth factors, including transforming growth factor (TGF)-β1, in the supernatants of high-affinity IgE receptor (FcεRI)-activated HLMCs which, when applied to ASM cells, impaired albuterol-induced cyclic adenosine monophosphate (cAMP) production, an effect that was prevented following neutralization of TGF-β1. This blunted β -AR response was reproduced by treating ASM cells with TGF-β1 or fibroblast growth factor (FGF)-2, which induced β -AR phosphorylation at tyrosine residues Tyr and Tyr , and significantly reduced the maximal bronchorelaxant responses to isoproterenol in human precision cut lung slices (PCLS). Finally, ASM cells isolated from severe asthmatics displayed constitutive elevated β -AR phosphorylation at both Tyr and Tyr and a reduced relaxant response to albuterol. This study shows for the first time that abnormal β -AR phosphorylation/function in ASM cells that is induced rapidly by HLMC-derived growth factors, is present constitutively in cells from severe asthmatics.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194334 | PMC |
| http://dx.doi.org/10.1111/cei.13191 | DOI Listing |
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