ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice
| العنوان: | ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice |
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| المؤلفون: | James K. Liao, Youngji Cho, Joel A. Mathews, Chan Young Park, Allison P. Wurmbrand, Stephanie A. Shore, David I. Kasahara, Gabrielle Hunt |
| المصدر: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 309:L736-L746 |
| بيانات النشر: | American Physiological Society, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, medicine.medical_specialty, RHOA, Physiology, Inflammation, Gene Expression Regulation, Enzymologic, Mice, Oxidants, Photochemical, Ozone, Physiology (medical), Internal medicine, medicine, Animals, Humans, ROCK1, ROCK2, Rho-associated protein kinase, rho-Associated Kinases, Dose-Response Relationship, Drug, biology, Tumor Necrosis Factor-alpha, Interleukin-17, Fasudil, Muscle, Smooth, Articles, Pneumonia, Cell Biology, respiratory system, Mice, Mutant Strains, respiratory tract diseases, Endocrinology, biology.protein, Osteopontin, Tumor necrosis factor alpha, Bronchial Hyperreactivity, medicine.symptom, Muscle Contraction, Muscle contraction |
| الوصف: | Ozone causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Rho kinase (ROCK) is a key regulator of smooth muscle cell contraction and inflammatory cell migration. To determine the contribution of the two ROCK isoforms ROCK1 and ROCK2 to ozone-induced AHR, we exposed wild-type, ROCK1+/−, and ROCK2+/− mice to air or ozone (2 ppm for 3 h) and evaluated mice 24 h later. ROCK1 or ROCK2 haploinsufficiency did not affect airway responsiveness in air-exposed mice but significantly reduced ozone-induced AHR, with a greater reduction in ROCK2+/− mice despite increased bronchoalveolar lavage (BAL) inflammatory cells in ROCK2+/− mice. Compared with wild-type mice, ozone-induced increases in BAL hyaluronan, a matrix protein implicated in ozone-induced AHR, were lower in ROCK1+/− but not ROCK2+/− mice. Ozone-induced increases in other inflammatory moieties reported to contribute to ozone-induced AHR (IL-17A, osteopontin, TNFα) were not different in wild-type vs. ROCK1+/− or ROCK2+/− mice. We also observed a dose-dependent reduction in ozone-induced AHR after treatment with the ROCK1/ROCK2 inhibitor fasudil, even though fasudil was administered after induction of inflammation. Ozone increased pulmonary expression of ROCK2 but not ROCK1 or RhoA. A ROCK2 inhibitor, SR3677, reduced contractile forces in primary human airway smooth muscle cells, confirming a role for ROCK2 in airway smooth muscle contraction. Our results demonstrate that ozone-induced AHR requires ROCK. Whereas ROCK1-dependent changes in hyaluronan may contribute to ROCK1's role in O3-induced AHR, the role of ROCK2 is downstream of inflammation, likely at the level of airway smooth muscle contraction. |
| تدمد: | 1522-1504 1040-0605 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::677db44af9d0ea867f23dd0af48b275c https://doi.org/10.1152/ajplung.00372.2014 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....677db44af9d0ea867f23dd0af48b275c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221504 10400605 |
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