| RRC ID |
46925
|
| Author |
Nagayoshi M, Tada Y, West J, Ochiai E, Watanabe A, Toyotome T, Tanabe N, Takiguchi Y, Shigeta A, Yasuda T, Shibuya K, Kamei K, Tatsumi K.
|
| Title |
Inhalation of Stachybotrys chartarum evokes pulmonary arterial remodeling in mice, attenuated by Rho-kinase inhibitor.
|
| Journal |
Mycopathologia
|
| Abstract |
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.
|
| Volume |
172(1)
|
| Pages |
5-15
|
| Published |
2011-7-1
|
| DOI |
10.1007/s11046-011-9400-3
|
| PMID |
21505873
|
| MeSH |
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / administration & dosage
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
Animals
Cytokines / metabolism
Disease Models, Animal
Lung / microbiology*
Lung / pathology*
Lung Diseases, Fungal / microbiology*
Lung Diseases, Fungal / pathology*
Male
Mice
Neovascularization, Pathologic*
Protein Kinase Inhibitors / administration & dosage
Rodent Diseases / microbiology
Rodent Diseases / pathology
Stachybotrys / pathogenicity*
Th2 Cells / immunology
rho-Associated Kinases / antagonists & inhibitors*
|
| IF |
2.452
|
| Times Cited |
12
|
|
WOS Category
|
MYCOLOGY
|
| Resource |
| Pathogenic microorganisms |
IFM 53637 |
