PMID- 27448781 OWN - NLM STAT- MEDLINE DCOM- 20171103 LR - 20220408 IS - 1944-7930 (Electronic) IS - 1539-6509 (Linking) VI - 21 IP - 118 DP - 2016 Jun TI - Curcumin protects against liver fibrosis by attenuating infiltration of Gr1hi monocytes through inhibition of monocyte chemoattractant protein-1. PG - 447-57 AB - BACKGROUND AND AIMS: 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). METHODS: 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)-alpha, interleukin (IL)-6, IL-1beta, and transforming growth factor (TGF)-beta1 were determined by real time PCR. Hepatic expression of MCP-1 was determined by real time PCR and immunohistochemistry. RESULTS: 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-alpha and TGF-beta1, which is in line with the decreased numbers of intrahepatic Gr1hi monocytes. Intrahepatic MCP-1 expression of CCl4-challenged mice was inhibited by curcumin. CONCLUSIONS: 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. FAU - Huang, Rui AU - Huang R AD - Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Liu, Yong AU - Liu Y AD - Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Xiong, Yali AU - Xiong Y AD - Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Wu, Hongyan AU - Wu H AD - Department of Pathology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Wang, Guiyang AU - Wang G AD - Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Sun, Zhenhua AU - Sun Z AD - Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Chen, Jin AU - Chen J AD - Department of Pathology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Yan, Xiaomin AU - Yan X AD - Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Pan, Zhiyun AU - Pan Z AD - Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Xia, Juan AU - Xia J AD - Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Zhang, Zhaoping AU - Zhang Z AD - Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Wang, Jinke AU - Wang J AD - State Key Laboratory of Bioelectronics, Southeast University, Nanjing, Jiangsu, China. FAU - Wu, Chao AU - Wu C AD - Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Discov Med JT - Discovery medicine JID - 101250006 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Antigens, Ly) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Ly-6C antigen, mouse) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Tumor Necrosis Factor-alpha) RN - CL2T97X0V0 (Carbon Tetrachloride) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use MH - Antigens, Ly/metabolism MH - Carbon Tetrachloride/toxicity MH - Chemokine CCL2/*metabolism MH - Curcumin/pharmacology/*therapeutic use MH - Disease Models, Animal MH - Flow Cytometry MH - Humans MH - Immunohistochemistry MH - Inflammation/metabolism/*prevention & control MH - Liver/pathology MH - Liver Cirrhosis/chemically induced/pathology/*prevention & control MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Monocytes/*drug effects/metabolism MH - Transforming Growth Factor beta1/metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2016/07/28 06:00 MHDA- 2017/11/04 06:00 CRDT- 2016/07/25 06:00 PHST- 2016/07/25 06:00 [entrez] PHST- 2016/07/28 06:00 [pubmed] PHST- 2017/11/04 06:00 [medline] PST - ppublish SO - Discov Med. 2016 Jun;21(118):447-57.