ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Advanced Microparticulate/Nanoparticulate Respirable Dry Powders of a Selective RhoA/Rho Kinase (Rock) Inhibitor for Targeted Pulmonary Inhalation Aerosol Delivery.Pharmaceutics · 2021Article
- Reciprocal Correlations of Inflammatory and Calcium Signaling in Asthma Pathogenesis.Advances in experimental medicine and biology · 2021Article
- Gut microbiota from androgen-altered donors alter pulmonary responses to ozone in female mice.Physiological reports · 2020Article
- IL-33, diet-induced obesity, and pulmonary responses to ozone.Respiratory research · 2020Article
- Androgens augment pulmonary responses to ozone in mice.Physiological reports · 2019Article
- The interleukin-33 receptor contributes to pulmonary responses to ozone in male mice: role of the microbiome.Respiratory research · 2019Article
- Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Transcriptional Effects of Ozone and Impact on Airway Inflammation.Frontiers in immunology · 2019Review
- High molecular weight hyaluronan ameliorates allergic inflammation and airway hyperresponsiveness in the mouse.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- The Rho Kinase Isoforms ROCK1 and ROCK2 Each Contribute to the Development of Experimental Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2018Article
- Effects of Simulated Smog Atmospheres in Rodent Models of Metabolic and Immunologic Dysfunction.Environmental science & technology · 2018Article
- Augmented Responses to Ozone in Obese Mice Require IL-17A and Gastrin-Releasing Peptide.American journal of respiratory cell and molecular biology · 2018Article
- Role of ROCK2 in CD4Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2017Article
- Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- The Next Generation of Risk Assessment Multi-Year Study-Highlights of Findings, Applications to Risk Assessment, and Future Directions.Environmental health perspectives · 2016Review
- Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone.Physiological reports · 2016Article
- Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure.Toxicology and applied pharmacology · 2016Article
- ROCK1 via LIM kinase regulates growth, maturation and actin based functions in mast cells.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.