Polyinosinic: Polycytidylic Acid (Poly I:C)-Induced Airway Inflammation Is Partially Inhibited By Budesonide

Harmatz, Paul; Peng, Ruoqi; Cohn, Ronald G.; Woods, John; Phillips, Jonathan E.; Burns, Lisa; Fine, Jay S.; Stevenson, Christopher S.

doi:10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a6200

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“…A limitation of our study is that we did not go beyond 50.0 mg/mL of MCh to assess the lung function. There are several reports that have described studies using more than 50.0 mg/mL of inhaled MCh to assess the lung function in mice (Harris et al 2011;Sunil et al 2011). We speculate that the compromised lung function we observed may be greater at concentrations of MCh higher than we used.…”

Section: Discussionmentioning

confidence: 66%

Characterization of the dystrophin–glycoprotein complex in airway smooth muscle: role of δ-sarcoglycan in airway responsiveness

Sharma

Jha

Stelmack

et al. 2015

Can. J. Physiol. Pharmacol.

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The dystrophin-glycoprotein complex (DGC) is an integral part of caveolae microdomains, and its interaction with caveolin-1 is essential for the phenotype and functional properties of airway smooth muscle (ASM). The sarcoglycan complex provides stability to the dystroglycan complex, but its role in ASM contraction and lung physiology in not understood. We tested whether δ-sarcoglycan (δ-SG), through its interaction with the DGC, is a determinant of ASM contraction ex vivo and airway mechanics in vivo. We measured methacholine (MCh)-induced isometric contraction and airway mechanics in δ-SG KO and wild-type mice. Last, we performed immunoblotting and transmission electron microscopy to assess DGC protein expression and the ultrastructural features of tracheal smooth muscle. Our results reveal an age-dependent reduction in the MCh-induced tracheal isometric force and significant reduction in airway resistance at high concentrations of MCh (50.0 mg/mL) in δ-SG KO mice. The changes in contraction and lung function correlated with decreased caveolin-1 and β-dystroglycan abundance, as well as an age-dependent loss of caveolae in the cell membrane of tracheal smooth muscle in δ-SG KO mice. Collectively, these results confirm and extend understanding of a functional role for the DGC in the contractile properties of ASM and demonstrate that this results in altered lung function in vivo.

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Section: Discussionmentioning

confidence: 66%