title: Cultured Mycelium Cordyceps sinensis allevi¬ates CCl4-induced liver inflammation and fibrosis in mice by activating hepatic natural killer cells.
abstract: OBJECTIVE
  Recent evidence shows that cultured mycelium Cordyceps sinensis (CMCS) effectively protects against liver fibrosis in mice. Here, we investigated whether the anti-fibrotic action of CMCS was related to its regulation of the activity of hepatic natural killer (NK) cells in CCl4-treated mice.
  
  
  METHODS
  C57BL/6 mice were injected with 10% CCl4 (2 mL/kg, ip) 3 times per week for 4 weeks, and received CMCS (120 mg·kg(-1)·d(-1), ig) during this period. In another part of experiments, the mice were also injected with an NK cell-deleting antibody ASGM-1 (20 μg, ip) 5 times in the first 3 weeks. After the mice were sacrificed, serum liver function, and liver inflammation, hydroxyproline content and collagen deposition were assessed. The numbers of hepatic NK cells and expression of NKG2D (activation receptor of NK cells) on isolated liver lymphocytes were analyzed using flow cytometry. Desmin expression and cell apoptosis in liver tissues were studied using desmin staining and TUNEL assay, respectively. The levels of α-SMA, TGF-β, RAE-1δ and RAE-1ε in liver tissues were determined by RT-qPCR.
  
  
  RESULTS
  In CCl4-treated mice, CMCS administration significantly improved liver function, attenuated liver inflammation and fibrosis, and increased the numbers of hepatic NK cells and expression level of NKG2D on hepatic NK cells. Furthermore, CMCS administration significantly decreased desmin expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Injection with NK cell-deleting ASGM-1 not only diminished the numbers of hepatic NK cells, but also greatly accelerated liver inflammation and fibrosis in CCl4-treated mice. In CCl4-treated mice with NK cell depletion, CMCS administration decelerated the rate of liver fibrosis development, and mildly upregulated the numbers of hepatic NK cells but without changing NKG2D expression.
  
  
  CONCLUSIONS
  CMCS alleviates CCl4-induced liver inflammation and fibrosis via promoting activation of hepatic NK cells. CMCS partially reverses ASGM-1-induced depletion of hepatic NK cells.
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai 201203, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Tao
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.|Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai 201203, China.|E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai 201203, China.
authors.forename: Cheng-hai
authors.initials: CH
authors.lastname: Liu
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D002251:Carbon Tetrachloride; D032661:Cordyceps / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D025282:Mycelium / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D004365:Drugs, Chinese Herbal; D002251:Carbon Tetrachloride