TY - JOUR T1 - Role of Rho Kinase Isoforms in Murine Allergic Airway Responses JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/09031936.00125010 SP - erj01250-2010 AU - M. Zhu AU - P-Y. Liu AU - D.I. Kasahara AU - A.S. Williams AU - N.G. Verbout AU - A.J. Halayko AU - A. Fedulov AU - T. Shoji AU - E.S. Williams AU - K. Noma AU - S.A. Shore AU - J.K. Liao Y1 - 2011/05/12 UR - http://erj.ersjournals.com/content/early/2011/05/12/09031936.00125010.abstract N2 - Inhibition of Rho-associated coiled-coil forming kinases (ROCKs) reduces allergic airway responses in mice. The purpose of this study was to determine the roles of the two ROCK isoforms, ROCK1 and ROCK2, in these responses.Wildtype mice and heterozygous ROCK1 and ROCK2 knockout mice (ROCK1+/− and ROCK2+/− respectively) were sensitized and challenged with ovalbumin. ROCK expression and activation were assessed by Western blotting. Airway responsiveness was measured by forced oscillation. Bronchoalveolar lavage was performed and the lungs were fixed for histological assessment.Compared to wildtype mice, ROCK1 and ROCK2 expression were 50% lower in lungs of ROCK1+/− and ROCK2+/− mice, respectively, without changes in the other isoform. In wildtype lungs, ROCK activation increased after ovalbumin challenge, was sustained for several hours, and was reduced in ROCK1+/− and ROCK2+/− lungs. Airway responsiveness was comparable in wildtype, ROCK1+/−, and ROCK2+/− mice challenged with PBS. Ovalbumin challenge caused airway hyperresponsiveness in wildtype, but not ROCK1+/− or ROCK2+/− mice. Lavage eosinophils and goblet cell hyperplasia were significantly reduced in ovalbumin-challenged ROCK1+/− and ROCK2+/− versus wildtype mice. Ovalbumin-induced changes in lavage interleukin-13, interleukin-5, and lymphocytes were also reduced in ROCK1+/− mice.Both ROCK1 and ROCK2 are important in regulating allergic airway responses. ER -