Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo.
Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1-induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1-treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin-induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-β1 in lung tissues, and this effect is accompanied by decreased collagen 3α1 and α-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis.
Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Laboratory of Nanomaterials, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
Tsung-Teng
TT
Huang
Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
Hsin-Chih
HC
Lai
Biochemical Engineering Research Center, Ming Chi University of Technology, New Taipei City 24301, Taiwan, ROC.|Chang Gung Biotechnology Corporation, Taipei 10508, Taiwan, ROC.
Yun-Fei
YF
Ko
Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, CA 94103, USA.
David M
DM
Ojcius
Graduate Institute of Biomedical Sciences, Division of Biotechnology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
Ying-Wei
YW
Lan
Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Laboratory of Nanomaterials, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
Jan
J
Martel
Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Laboratory of Nanomaterials, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Biochemical Engineering Research Center, Ming Chi University of Technology, New Taipei City 24301, Taiwan, ROC.|Chang Gung Biotechnology Corporation, Taipei 10508, Taiwan, ROC.|Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021, USA.
John D
JD
Young
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Graduate Institute of Biomedical Sciences, Division of Biotechnology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC.|Department of Family Medicine, Chang Gung Memorial Hospital-Linkou, Taoyuan 33305, Taiwan, ROC.
Kowit-Yu
KY
Chong
D000818:Animals; D001203:Ascomycota / Q000502:physiology*; D001761:Bleomycin / Q000633:toxicity*; D006801:Humans; D051379:Mice; D025282:Mycelium / Q000502:physiology*; D011014:Pneumonia / Q000139:chemically induced*; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D013482:Superoxide Dismutase / Q000378:metabolism
D001761:Bleomycin; D013482:Superoxide Dismutase