PMID- 25122558
OWN - NLM
STAT- MEDLINE
DCOM- 20150204
LR  - 20211021
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 28
IP  - 12
DP  - 2014 Dec
TI  - Protective role of macrophage migration inhibitory factor in nonalcoholic 
      steatohepatitis.
PG  - 5136-47
LID - 10.1096/fj.14-256776 [doi]
AB  - MIF is an inflammatory cytokine but is hepatoprotective in models of 
      hepatotoxin-induced liver fibrosis. Hepatic fibrosis can also develop from 
      metabolic liver disease, such as nonalcoholic fatty liver disease (NASH). We 
      investigated the role of MIF in high-fat or methionine- and choline-deficient 
      diet mouse models of NASH. Mif(-/-) mice showed elevated liver triglyceride 
      levels (WT, 53+/-14 mg/g liver; Mif(-/-), 103+/-7 mg/g liver; P<0.05) and a 2-3-fold 
      increased expression of lipogenic genes. Increased fatty degeneration in the 
      livers of Mif(-/-) mice was associated with increased hepatic inflammatory cells 
      (1.6-fold increase in F4/80(+) macrophages) and proinflammatory cytokines (e.g., 
      2.3-fold increase in Tnf-alpha and 2-fold increase in Il-6 expression). However, 
      inflammatory cells and cytokines were decreased by 50-90% in white adipose tissue 
      (WAT) of Mif(-/-) mice. Subset analysis showed that macrophage phenotypes in 
      livers of Mif(-/-) mice were skewed toward M2 (e.g., 1.7-fold and 2.5-fold 
      increase in Arg1 and Il-13, respectively, and 2.5-fold decrease in iNos), whereas 
      macrophages were generally reduced in WAT of these mice (70% reduction in mRNA 
      expression of F4/80(+) macrophages). The protective MIF effect was scrutinized in 
      isolated hepatocytes. MIF reversed inflammation-induced triglyceride accumulation 
      in Hepa1-6 cells and primary hepatocytes and also attenuated oleic acid-elicited 
      triglyceride increase in 3T3-L1 adipocytes. Protection from fatty hepatocyte 
      degeneration was paralleled by a 2- to 3-fold reduction by MIF of hepatocyte 
      proinflammatory cytokine production. Blockade of MIF receptor cluster of 
      differentiation 74 (CD74) but not of CXCR2 or CXCR4 fully reverted the protective 
      effect of MIF, comparable to AMPK inhibition. In summary, we demonstrate that MIF 
      mediates hepatoprotection through the CD74/AMPK pathway in hepatocytes in 
      metabolic models of liver injury.
CI  - (c) FASEB.
FAU - Heinrichs, Daniel
AU  - Heinrichs D
AD  - Institute of Biochemistry and Molecular Cell Biology and Department of Internal 
      Medicine III, Rheinisch-Westfaelische Technische Hochschule (RWTH) Aachen 
      University, Aachen, Germany; and.
FAU - Berres, Marie-Luise
AU  - Berres ML
AD  - Department of Internal Medicine III, Rheinisch-Westfaelische Technische 
      Hochschule (RWTH) Aachen University, Aachen, Germany; and.
FAU - Coeuru, Melanie
AU  - Coeuru M
AD  - Institute of Biochemistry and Molecular Cell Biology and.
FAU - Knauel, Meike
AU  - Knauel M
AD  - Institute of Biochemistry and Molecular Cell Biology and.
FAU - Nellen, Andreas
AU  - Nellen A
AD  - Department of Internal Medicine III, Rheinisch-Westfaelische Technische 
      Hochschule (RWTH) Aachen University, Aachen, Germany; and.
FAU - Fischer, Petra
AU  - Fischer P
AD  - Department of Internal Medicine III, Rheinisch-Westfaelische Technische 
      Hochschule (RWTH) Aachen University, Aachen, Germany; and.
FAU - Philippeit, Claudia
AU  - Philippeit C
AD  - Institute of Biochemistry and Molecular Cell Biology and.
FAU - Bucala, Richard
AU  - Bucala R
AD  - Department of Internal Medicine, Yale University School of Medicine, New Haven, 
      Connecticut, USA.
FAU - Trautwein, Christian
AU  - Trautwein C
AD  - Department of Internal Medicine III, Rheinisch-Westfaelische Technische 
      Hochschule (RWTH) Aachen University, Aachen, Germany; and.
FAU - Wasmuth, Hermann E
AU  - Wasmuth HE
AD  - Department of Internal Medicine III, Rheinisch-Westfaelische Technische 
      Hochschule (RWTH) Aachen University, Aachen, Germany; and.
FAU - Bernhagen, Jurgen
AU  - Bernhagen J
AD  - Institute of Biochemistry and Molecular Cell Biology and jbernhagen@ukaachen.de.
LA  - eng
GR  - R01 AI042310/AI/NIAID NIH HHS/United States
GR  - R56 AI042310/AI/NIAID NIH HHS/United States
GR  - AI042310/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140813
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (DNA Primers)
RN  - 0 (Macrophage Migration-Inhibitory Factors)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers
MH  - Disease Models, Animal
MH  - Macrophage Migration-Inhibitory Factors/genetics/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Non-alcoholic Fatty Liver Disease/*prevention & control
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC4232286
OTO - NOTNLM
OT  - cytokines
OT  - fatty liver
OT  - hepatic fibrosis
OT  - hepatocyte
OT  - inflammation
EDAT- 2014/08/15 06:00
MHDA- 2015/02/05 06:00
PMCR- 2015/12/01
CRDT- 2014/08/15 06:00
PHST- 2014/08/15 06:00 [entrez]
PHST- 2014/08/15 06:00 [pubmed]
PHST- 2015/02/05 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - fj.14-256776 [pii]
AID - 14-256776 [pii]
AID - 10.1096/fj.14-256776 [doi]
PST - ppublish
SO  - FASEB J. 2014 Dec;28(12):5136-47. doi: 10.1096/fj.14-256776. Epub 2014 Aug 13.