PMID- 25074471
OWN - NLM
STAT- MEDLINE
DCOM- 20150708
LR  - 20211203
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 128
IP  - 4
DP  - 2015 Feb
TI  - CXCR4 dysfunction in non-alcoholic steatohepatitis in mice and patients.
PG  - 257-67
LID - 10.1042/CS20130833 [doi]
AB  - Homing of inflammatory cells to the liver is key in the progression of 
      non-alcoholic steatohepatitis (NASH). An abnormal response of CD4+ T-cells from 
      obese mice to the chemotactic effect of CXCL12 has been reported but the 
      mechanism involved in this process and relevance in patients are unknown. We 
      aimed to explore the mechanism involved in the abnormal chemotaxis of CXC 
      chemokine ligand 12 (CXCL12) in several mouse models of NASH and the relevance in 
      the context of human non-alcoholic fatty liver disease (NAFLD). We assessed 
      chemotactic responsiveness of CD4+ T-cells to CXCL12, the effect of AMD3100, a 
      CXC chemokine receptor 4 (CXCR4) antagonist, in mice and lymphocytes from 
      patients with NAFLD, and the affinity of CXCL12 for CXCR4. CXCL12-promoted 
      migration of CD4+ T-cells from three different mouse models of NASH was increased 
      and dependent of CXCR4. CD4+ T-cells from patients with NASH, but not from 
      patients with pure steatosis, responded more strongly to the chemotactic effect 
      of CXCL12, and this response was inhibited by AMD3100. Treatment with AMD3100 
      decreased the number of CD4+ T-cells to the liver in ob/ob mice. CXCL12 
      expression in the liver, CXCR4 and CXCR7 expression in CD4+ T-cells were not 
      increased in three different mouse models of NASH. However, the affinity of 
      CXCL12 for CXCR4 was increased in CD4+ T-cells of ob/ob mice. In conclusion, the 
      CXCL12/CXCR4 pathway contributes in both mice and patients to the enhanced 
      recruitment of CD4+ T-cells in NASH. An increased affinity of CXCL12 to CXCR4 
      rather than a higher expression of the chemokine or its receptors is involved in 
      this process.
FAU - Boujedidi, Hedia
AU  - Boujedidi H
FAU - Robert, Olivier
AU  - Robert O
FAU - Bignon, Alexandre
AU  - Bignon A
FAU - Cassard-Doulcier, Anne-Marie
AU  - Cassard-Doulcier AM
FAU - Renoud, Marie-Laure
AU  - Renoud ML
AD  - daggerINSERM U996, Clamart, France.
FAU - Gary-Gouy, Helene
AU  - Gary-Gouy H
AD  - daggerINSERM U996, Clamart, France.
FAU - Hemon, Patrice
AU  - Hemon P
AD  - daggerINSERM U996, Clamart, France.
FAU - Tharinger, Hugo
AU  - Tharinger H
AD  - daggerINSERM U996, Clamart, France.
FAU - Prevot, Sophie
AU  - Prevot S
FAU - Bachelerie, Francoise
AU  - Bachelerie F
FAU - Naveau, Sylvie
AU  - Naveau S
FAU - Emilie, Dominique
AU  - Emilie D
FAU - Balabanian, Karl
AU  - Balabanian K
FAU - Perlemuter, Gabriel
AU  - Perlemuter G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Benzylamines)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cmkor1 protein, mouse)
RN  - 0 (Cyclams)
RN  - 0 (Heterocyclic Compounds)
RN  - 0 (Receptors, CXCR)
RN  - 0 (Receptors, CXCR4)
RN  - S915P5499N (plerixafor)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Benzylamines
MH  - CD4-Positive T-Lymphocytes/cytology/drug effects
MH  - Cell Movement/drug effects
MH  - Chemokine CXCL12/pharmacology
MH  - Cyclams
MH  - Disease Models, Animal
MH  - Female
MH  - Heterocyclic Compounds/pharmacology
MH  - Humans
MH  - Lymphocyte Count
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Middle Aged
MH  - Non-alcoholic Fatty Liver Disease/*metabolism/pathology
MH  - Receptors, CXCR/metabolism
MH  - Receptors, CXCR4/*metabolism
MH  - Up-Regulation/drug effects
EDAT- 2014/07/31 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/07/31 06:00
PHST- 2014/07/31 06:00 [entrez]
PHST- 2014/07/31 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - CS20130833 [pii]
AID - 10.1042/CS20130833 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2015 Feb;128(4):257-67. doi: 10.1042/CS20130833.