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
Pathogenic microorganisms IFM 53637