Document Detail


Inhalation of Stachybotrys chartarum evokes pulmonary arterial remodeling in mice, attenuated by Rho-kinase inhibitor.
MedLine Citation:
PMID:  21505873     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-20
Journal Detail:
Title:  Mycopathologia     Volume:  172     ISSN:  1573-0832     ISO Abbreviation:  Mycopathologia     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-22     Completed Date:  2011-11-08     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  7505689     Medline TA:  Mycopathologia     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  5-15     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / 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:
R01 HL082694/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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:
Mycopathologia. 2011 Jul;172(1):1-3   [PMID:  21505872 ]

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