Suppression of airway hyperresponsiveness induced by ovalbumin sensitisation and RSV infection with Y-27632, a Rho kinase inhibitor

Hashimoto, K.; Peebles Jr., R. S.; Sheller, J. R.; Jarzecka, K.; Furlong, J.; Mitchell, D. B.; Hortert, T. V.; Graham, B. S.; Peebles, R S Jr; Hartert, T V
June 2002
Thorax;Jun2002, Vol. 57 Issue 6, p524
Academic Journal
journal article
Background: Smooth muscle contraction is one of the hallmarks of asthma. A recently developed pyridine derivative, Y-27632, a selective Rho kinase inhibitor, has been reported to inhibit the smooth muscle contraction of human and animal trachea in ex vivo systems but its effect in animal models of airway hyperresponsiveness (AHR) has not been examined. The purpose of this study was to evaluate the effect of Y-27632 in a murine model of allergic and virally induced AHR.Methods: Baseline lung resistance and methacholine induced AHR were measured in mice sensitised to ovalbumin (OVA) and also in mice infected with respiratory syncytial virus (RSV) following ovalbumin sensitisation (OVA/RSV).Results: Time course and dose ranging experiments indicated that 30 mg/kg Y-27632 given by gavage 2 hours before methacholine challenge significantly reduced baseline lung resistance and prevented AHR in OVA sensitised mice. Y-27632 also suppressed AHR induced by the bronchospastic agent serotonin in OVA sensitised mice and prevented methacholine induced AHR in OVA/RSV mice.Conclusions: These results suggest that the signalling pathway mediated through Rho kinase may have an important role in bronchial smooth muscle tone in allergen induced and virus induced AHR and should be considered as a novel target for asthma treatment.


Related Articles

  • RhoA/Rho-Kinase as a Therapeutic Target in Asthma. Kume, Hiroaki // Current Medicinal Chemistry;2008, Vol. 15 Issue 27, p2876 

    Rho-kinase is an effector molecule of RhoA, a monomeric GTP-binding protein, and causes Ca2+ sensitization via inactivation of myosin phosphatase. The major physiological functions of Rho-kinase include contraction, migration, and proliferation in cells. These actions are thought to be related...

  • Inhalation of the Rho-kinase inhibitor Y-27632 reverses allergen-induced airway hyperresponsiveness after the early and late asthmatic reaction. Schaafsma, Dedmer; Bos, I. Sophie T.; Zuidhof, Annet B.; Zaagsma, Johan; Meurs, Herman // Respiratory Research;2006, Vol. 7, p121 

    Background: In guinea pigs, we have previously demonstrated that the contribution of Rho-kinase to airway responsiveness in vivo and ex vivo is enhanced after active sensitization with ovalbumin (OA). Using conscious, unrestrained OA-sensitized guina pigs, we now investigated the role of...

  • Dual Effects of Respiratory Syncytial Virus Infections on Airway Inflammation by Regulation of Th17/Treg Responses in Ovalbumin-Challenged Mice. Wang, Jia; Kong, Lingwen; Luo, Qingli; Li, Bei; Wu, Jinfeng; Liu, Baojun; Wu, Xiao; Dong, Jingcheng // Inflammation;Dec2014, Vol. 37 Issue 6, p1984 

    We investigated the effects of respiratory syncytial virus (RSV) infections on ovalbumin (OVA)-challenged mice via regulation of Th17/Treg cell responses. BALB/c mice were challenged with OVA, followed by RSV infections twice. In OVA-challenged mice, the secretion of Th2/Th17-type cytokines,...

  • Immune Interaction between Respiratory Syncytial Virus Infection and Allergen Sensitization Critically Depends on Timing of Challenges. Peebles Jr., R. Stokes; Hashimoto, Koichi; Collins, Rober D.; Jarzecka, Kasia; Furlong, Jamye; Mitchell, Daphne B.; Sheller, James R.; Graham, Barney S. // Journal of Infectious Diseases;12/1/2001, Vol. 184 Issue 11, p1374 

    Severe respiratory syncytial virus (RSV) infection has been hypothesized to be a risk factor for the development of allergy and asthma, but epidemiologic studies in humans have been inconclusive. By use of a well-characterized murine model of RSV infection and allergic sensi-tization with...

  • Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice. Siegle, Jessica S.; Hansbro, Nicole; Herbert, Cristan; Rosenberg, Helene F.; Domachowske, Joseph B.; Asquith, Kelly L.; Foster, Paul S.; Kumar, Rakesh K. // Respiratory Research;2010, Vol. 11, p14 

    Background: Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV), increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen...

  • Respiratory Syncytial Virus Reverses Airway Hyperresponsiveness to Methacholine in Ovalbumin- Sensitized Mice. Aeffner, Famke; Davis, Ian C. // PLoS ONE;Oct2012, Vol. 7 Issue 10, Special section p1 

    Each year, approximately 20% of asthmatics in the United States experience acute symptom exacerbations, which commonly result from pulmonary viral infections. The majority of asthma exacerbations in very young children follow infection with respiratory syncytial virus (RSV). However, pathogenic...

  • The Extract of Cordyceps sinensis Inhibited Airway Inflammation by Blocking NF-κB Activity. Chiou, Ya-Ling; Lin, Ching-Yuang // Inflammation;Jun2012, Vol. 35 Issue 3, p985 

    Aiming the extract of Cordyceps sinensis significantly inhibits airway inflammation, airway hyperresponsiveness, and the infiltration of eosinophils in the airway of rats and may be related to the modulation of T helper (Th)1 and Th2 cells functions. The mechanisms of C. sinensis involved in...

  • Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease. Alison N Thorburn // Thorax;Dec2010, Vol. 65 Issue 12, p1053 

    BACKGROUND: Infections with some bacteria, including Streptococcus pneumoniae, have been associated with a reduced incidence of asthma. Components of S pneumoniae may have the potential to modulate allergic inflammatory responses and suppress the development of asthma. OBJECTIVES: To determine...

  • Role of Abl in airway hyperresponsiveness and airway remodeling. Cleary, Rachel A.; Ruping Wang; Tao Wang; Dale D. Tang // Respiratory Research;Oct2013, Vol. 14 Issue 10, p1 

    Background: Asthma is a chronic disease that is characterized by airway hyperresponsiveness and airway remodeling. The underlying mechanisms that mediate the pathological processes are not fully understood. Abl is a non-receptor protein tyrosine kinase that has a role in the regulation of smooth...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics