Role of Rho kinase isoforms in murine allergic airway responses

M. Zhu, P. Y. Liu, D. I. Kasahara, A. S. Williams, N. G. Verbout, A. J. Halayko, A. Fedulov, T. Shoji, E. S. Williams, K. Noma, S. A. Shore, J. K. Liao

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 (WT)mice and heterozygousROCK1 andROCK2 knockoutmice (ROCK1 +/- and ROCK2 +/-, respectively) were sensitised 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 with WT mice, ROCK1 and ROCK2 expression were 50% lower in lungs of ROCK1 +/-and ROCK2 +/- mice, respectively, without changes in the other isoform. In WT lungs, ROCK activation increased after ovalbumin challenge and was sustained for several hours. This activation was reduced in ROCK1 +/- and ROCK2 +/- lungs. Airway responsiveness was comparable in WT, ROCK1 +/-, and ROCK2 +/- mice challenged with PBS. Ovalbumin challenge caused airway hyperresponsiveness in WT, but not ROCK1 +/- or ROCK2 +/- mice. Lavage eosinophils and goblet cell hyperplasia were significantly reduced in ovalbumin-challenged ROCK1 +/- and ROCK2 +/- versus WT mice. Ovalbumin-induced changes in lavage interleukin-13, interleukin-5 and lymphocytes were also reduced in ROCK1 +/- mice. In conclusion, both ROCK1 and ROCK2 are important in regulating allergic airway responses. Copyright

Original languageEnglish
Pages (from-to)841-850
Number of pages10
JournalEuropean Respiratory Journal
Volume38
Issue number4
DOIs
Publication statusPublished - 2011 Oct 1

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rho-Associated Kinases
Protein Isoforms
Ovalbumin
Lung
Therapeutic Irrigation
Goblet Cells
Interleukin-13
Interleukin-5
Bronchoalveolar Lavage
Eosinophils
Hyperplasia
Western Blotting
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Cite this

Zhu, M., Liu, P. Y., Kasahara, D. I., Williams, A. S., Verbout, N. G., Halayko, A. J., ... Liao, J. K. (2011). Role of Rho kinase isoforms in murine allergic airway responses. European Respiratory Journal, 38(4), 841-850. https://doi.org/10.1183/09031936.00125010
Zhu, M. ; Liu, P. Y. ; Kasahara, D. I. ; Williams, A. S. ; Verbout, N. G. ; Halayko, A. J. ; Fedulov, A. ; Shoji, T. ; Williams, E. S. ; Noma, K. ; Shore, S. A. ; Liao, J. K. / Role of Rho kinase isoforms in murine allergic airway responses. In: European Respiratory Journal. 2011 ; Vol. 38, No. 4. pp. 841-850.
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abstract = "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 (WT)mice and heterozygousROCK1 andROCK2 knockoutmice (ROCK1 +/- and ROCK2 +/-, respectively) were sensitised 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 with WT mice, ROCK1 and ROCK2 expression were 50{\%} lower in lungs of ROCK1 +/-and ROCK2 +/- mice, respectively, without changes in the other isoform. In WT lungs, ROCK activation increased after ovalbumin challenge and was sustained for several hours. This activation was reduced in ROCK1 +/- and ROCK2 +/- lungs. Airway responsiveness was comparable in WT, ROCK1 +/-, and ROCK2 +/- mice challenged with PBS. Ovalbumin challenge caused airway hyperresponsiveness in WT, but not ROCK1 +/- or ROCK2 +/- mice. Lavage eosinophils and goblet cell hyperplasia were significantly reduced in ovalbumin-challenged ROCK1 +/- and ROCK2 +/- versus WT mice. Ovalbumin-induced changes in lavage interleukin-13, interleukin-5 and lymphocytes were also reduced in ROCK1 +/- mice. In conclusion, both ROCK1 and ROCK2 are important in regulating allergic airway responses. Copyright",
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Zhu, M, Liu, PY, Kasahara, DI, Williams, AS, Verbout, NG, Halayko, AJ, Fedulov, A, Shoji, T, Williams, ES, Noma, K, Shore, SA & Liao, JK 2011, 'Role of Rho kinase isoforms in murine allergic airway responses', European Respiratory Journal, vol. 38, no. 4, pp. 841-850. https://doi.org/10.1183/09031936.00125010

Role of Rho kinase isoforms in murine allergic airway responses. / Zhu, M.; Liu, P. Y.; Kasahara, D. I.; Williams, A. S.; Verbout, N. G.; Halayko, A. J.; Fedulov, A.; Shoji, T.; Williams, E. S.; Noma, K.; Shore, S. A.; Liao, J. K.

In: European Respiratory Journal, Vol. 38, No. 4, 01.10.2011, p. 841-850.

Research output: Contribution to journalArticle

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AU - Liu, P. Y.

AU - Kasahara, D. I.

AU - Williams, A. S.

AU - Verbout, N. G.

AU - Halayko, A. J.

AU - Fedulov, A.

AU - Shoji, T.

AU - Williams, E. S.

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AU - Shore, S. A.

AU - Liao, J. K.

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