PMID- 27273604 OWN - NLM STAT- MEDLINE DCOM- 20180411 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Jun 8 TI - Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury. PG - 27665 LID - 10.1038/srep27665 [doi] LID - 27665 AB - Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation. FAU - Xie, Jieshi AU - Xie J AD - Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China. FAU - Yang, Le AU - Yang L AD - Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China. FAU - Tian, Lei AU - Tian L AD - Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China. FAU - Li, Weiyang AU - Li W AD - Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China. FAU - Yang, Lin AU - Yang L AD - Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China. FAU - Li, Liying AU - Li L AD - Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160608 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Biomarkers) RN - 0 (Chemokine CCL2) RN - 0 (Macrophage Migration-Inhibitory Factors) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - CL2T97X0V0 (Carbon Tetrachloride) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - *Autocrine Communication MH - Biomarkers MH - Carbon Tetrachloride/adverse effects MH - Chemical and Drug Induced Liver Injury/genetics/metabolism MH - Chemokine CCL2/*genetics/metabolism MH - Disease Models, Animal MH - *Gene Expression Regulation MH - Hepatocytes/*metabolism MH - Liver Diseases/*genetics/*metabolism/pathology MH - Macrophage Migration-Inhibitory Factors/*metabolism MH - Mice MH - Phosphorylation MH - Protein Kinase Inhibitors/pharmacology MH - RNA, Messenger/genetics/metabolism MH - Signal Transduction/drug effects MH - p38 Mitogen-Activated Protein Kinases/metabolism PMC - PMC4897699 EDAT- 2016/06/09 06:00 MHDA- 2018/04/12 06:00 PMCR- 2016/06/08 CRDT- 2016/06/09 06:00 PHST- 2016/02/15 00:00 [received] PHST- 2016/05/24 00:00 [accepted] PHST- 2016/06/09 06:00 [entrez] PHST- 2016/06/09 06:00 [pubmed] PHST- 2018/04/12 06:00 [medline] PHST- 2016/06/08 00:00 [pmc-release] AID - srep27665 [pii] AID - 10.1038/srep27665 [doi] PST - epublish SO - Sci Rep. 2016 Jun 8;6:27665. doi: 10.1038/srep27665.