title: Curcumin protects against liver fibrosis by attenuating infiltration of Gr1hi monocytes through inhibition of monocyte chemoattractant protein-1.
abstract: Liver fibrosis is concomitant with monocyte infiltration, which has been highlighted as novel therapeutic targets for chronic liver diseases. We aimed to investigate whether curcumin might protect the liver from carbon tetrachloride (CCl4)-induced fibrosis by attenuating the recruitment of Gr1hi monocytes through inhibition of monocyte chemoattractant protein-1 (MCP-1).
  
  
  
  Mice were intraperitoneally injected with CCl4 to induce liver fibrosis. Curcumin was orally administrated to mice. Hepatic inflammation and fibrosis were evaluated by analysis of liver function and hepatic histopathology. Infiltration of the Gr1hi monocytes was assessed by flow cytometry and immunohistochemistry. Moreover, mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β1 were determined by real time PCR. Hepatic expression of MCP-1 was determined by real time PCR and immunohistochemistry.
  
  
  
  Curcumin significantly attenuated inflammation and fibrosis, as revealed by histological and biochemical analysis. The intrahepatic infiltration of Gr1hi monocytes was attenuated by curcumin administration. T cells, NK cells, NKT cells, and dendritic cells were not affected by curcumin. Curcumin significantly reduced the expression of TNF-α and TGF-β1, which is in line with the decreased numbers of intrahepatic Gr1hi monocytes. Intrahepatic MCP-1 expression of CCl4-challenged mice was inhibited by curcumin.
  
  
  
  The anti-inflammatory and antifibrotic effects of curcumin could be contributed to its prevention of Gr1hi monocyte infiltration into the injured livers through inhibition of MCP-1. These new findings extend our understanding on the mechanisms of the anti-inflammatory and antifibrotic effects of curcumin.
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Pathology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Pathology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Jinke
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000950:Antigens, Ly / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D018932:Chemokine CCL2 / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000950:Antigens, Ly; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C494192:Ly-6C antigen, mouse; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride; D003474:Curcumin