Rho-kinase and contractile apparatus proteins in murine airway hyperresponsiveness

Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie
Martin WitzenrathHartwig Schütte

Abstract

Airway hyperresponsiveness (AHR) is a hallmark of bronchial asthma. Increased expression of smooth muscle contractile proteins or increased responsiveness of the contractile apparatus due to RhoA/Rho-kinase activation may contribute to AHR. BALB/c mice developed AHR following systemic sensitization by intraperitoneal injections of 20 microg ovalbumin (OVA) in presence of 2mg Al(OH)(3) on days 1 and 14, and airway challenge by 1% OVA-inhalation for 20 min each on days 28, 29 and 30. As assessed by Western blot, protein expression of RhoA, MLC (myosin light chain) and smMLCK (smooth muscle myosin light chain kinase) was increased in lungs of OVA/OVA-animals with AHR, as well as in lungs of OVA-sensitized and sham-challenged animals (OVA/PBS) without AHR, compared with lungs of PBS/PBS-animals. Pretreatment with the specific Rho-kinase inhibitor Y-27632 reduced MLC-phosphorylation and AHR. Contribution of Rho-kinase to bronchoconstriction was increased in lungs of OVA/OVA-animals compared with OVA/PBS- and PBS/PBS-animals, respectively. Furthermore, bronchoconstriction following MCh stimulation was significantly reduced after Y-27632 application. In conclusion, systemic allergen-sensitization increased pulmonary expression of prot...Continue Reading

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Citations

Apr 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Sophie J BradleyAndrew B Tobin
May 4, 2013·Current Opinion in Pharmacology·William T GerthofferBlanca Camoretti-Mercado
Apr 18, 2014·Scientific Reports·Katharine C PikeJohn W Holloway
Sep 25, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Samantha Souza PossaIolanda de Fátima Lopes Calvo Tibério
Sep 21, 2018·Frontiers in Physiology·Tabata M Dos SantosIolanda F L C Tibério

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