| Inhalation of Stachybotrys chartarum evokes pulmonary arterial remodeling in mice, attenuated by Rho-kinase inhibitor. | |
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MedLine Citation:
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PMID: 21505873 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Stachybotrys chartarum, a ubiquitous fungus in our environment, has been suspected of causing respiratory symptoms in humans, such as acute infant pulmonary hemorrhage and asthma. We previously established a mouse model in which repeated inhalation of Stachybotrys chartarum spores caused pulmonary hypertension. To further investigate the model, particularly in the pulmonary circulation, mice were intra-tracheally injected with spores, 18 times over 12 weeks. Severe muscularization was observed in the small- to medium-sized pulmonary arteries. Bronchoalveolar lavage fluid revealed an increase in eosinophils accompanied by high concentrations of Th2-associated cytokines, IL-4, IL-5, but not Th1-associated IFN-γ. The remodeling was temporary, resolving after cessation of spore inhalation. Chronic inhibition of the RhoA/Rho-kinase pathway by fasudil attenuated pulmonary arterial remodeling. These data suggest that Stachybotrys-mediated remodeling is caused by Th2-associated inflammation and can be resolved by Rho-kinase inhibition, either through direct effects on smooth muscle hypertrophy or through indirect effects on vascular inflammation. These data also show that extensive pulmonary vascular remodeling, often thought of as a fixed lesion, will spontaneously resolve in the absence of underlying molecular etiology. |
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Authors:
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Masaru Nagayoshi; Yuji Tada; James West; Eri Ochiai; Akira Watanabe; Takahito Toyotome; Nobuhiro Tanabe; Yuichi Takiguchi; Ayako Shigeta; Tadashi Yasuda; Kazutoshi Shibuya; Katsuhiko Kamei; Koichiro Tatsumi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-04-20 |
Journal Detail:
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Title: Mycopathologia Volume: 172 ISSN: 1573-0832 ISO Abbreviation: Mycopathologia Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-07-22 Completed Date: 2011-11-08 Revised Date: 2013-05-06 |
Medline Journal Info:
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Nlm Unique ID: 7505689 Medline TA: Mycopathologia Country: Netherlands |
Other Details:
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Languages: eng Pagination: 5-15 Citation Subset: IM |
Affiliation:
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Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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administration & dosage,
analogs & derivatives Animals Cytokines / secretion Disease Models, Animal Lung / microbiology*, pathology* Lung Diseases, Fungal / microbiology*, pathology* Male Mice Neovascularization, Pathologic* Protein Kinase Inhibitors / administration & dosage Rodent Diseases / microbiology, pathology Stachybotrys / pathogenicity* Th2 Cells / immunology rho-Associated Kinases / antagonists & inhibitors* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL082694/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Protein Kinase Inhibitors; 103745-39-7/fasudil; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; EC 2.7.11.1/rho-Associated Kinases |
| Comments/Corrections | |
Comment In:
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Mycopathologia. 2011 Jul;172(1):1-3
[PMID:
21505872
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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