PMID- 27609269
OWN - NLM
STAT- MEDLINE
DCOM- 20170817
LR  - 20171121
IS  - 1872-8421 (Electronic)
IS  - 0165-5728 (Linking)
VI  - 298
DP  - 2016 Sep 15
TI  - The immunomodulatory effect of laquinimod in CNS autoimmunity is mediated by the 
      aryl hydrocarbon receptor.
PG  - 9-15
LID - S0165-5728(16)30135-7 [pii]
LID - 10.1016/j.jneuroim.2016.06.003 [doi]
AB  - Though several functional properties of laquinimod have been identified, our 
      understanding of the underlying mechanisms is still incomplete. Since the 
      compound elicits similar immunomodulatory effects to ligands of the aryl 
      hydrocarbon receptor (AhR), we compared the efficacy of laquinimod in 
      experimental autoimmune encephalomyelitis (EAE)-afflicted wild-type and 
      AhR-deficient mice. Laquinimod failed to ameliorate clinical symptoms and 
      leukocyte infiltration in AhR-deficient mice; however, treatment exerted 
      neuroprotection by elevation of brain-derived neurotrophic factor (BDNF) 
      independent of genetic profile. Thus, our data identify the AhR pathway in these 
      mutant mice as crucial for the immunomodulatory, but not neuroprotective, 
      efficacy of laquinimod in EAE.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Berg, Johannes
AU  - Berg J
AD  - Department of Neurology, Ruhr-Universitat Bochum, 44801 Bochum, Germany.
FAU - Mahmoudjanlou, Yasaman
AU  - Mahmoudjanlou Y
AD  - Department of Neurology, Ruhr-Universitat Bochum, 44801 Bochum, Germany.
FAU - Duscha, Alexander
AU  - Duscha A
AD  - Department of Neurology, Ruhr-Universitat Bochum, 44801 Bochum, Germany.
FAU - Massa, Megan G
AU  - Massa MG
AD  - Department of Neurology, Ruhr-Universitat Bochum, 44801 Bochum, Germany.
FAU - Thone, Jan
AU  - Thone J
AD  - Department of Neurology, Ruhr-Universitat Bochum, 44801 Bochum, Germany.
FAU - Esser, Charlotte
AU  - Esser C
AD  - Leibniz-Research Institute for Environmental Medicine, 40225 Dusseldorf, Germany.
FAU - Gold, Ralf
AU  - Gold R
AD  - Department of Neurology, Ruhr-Universitat Bochum, 44801 Bochum, Germany. 
      Electronic address: ralf.gold@rub.de.
FAU - Haghikia, Aiden
AU  - Haghikia A
AD  - Department of Neurology, Ruhr-Universitat Bochum, 44801 Bochum, Germany. 
      Electronic address: aiden.haghikia@rub.de.
LA  - eng
PT  - Journal Article
DEP - 20160609
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CD3 Complex)
RN  - 0 (Immunologic Factors)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Peptide Fragments)
RN  - 0 (Quinolones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (myelin oligodendrocyte glycoprotein (35-55))
RN  - 908SY76S4G (laquinimod)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Axons/drug effects/pathology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - CD3 Complex/metabolism
MH  - Demyelinating Autoimmune Diseases, CNS/chemically induced/*drug 
      therapy/*immunology
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Immunologic Factors/*therapeutic use
MH  - Leukemic Infiltration/drug therapy
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myelin-Oligodendrocyte Glycoprotein/toxicity
MH  - Peptide Fragments/toxicity
MH  - Quinolones/*therapeutic use
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptors, Aryl Hydrocarbon/genetics/*metabolism
MH  - Spinal Cord/pathology
MH  - T-Lymphocytes/drug effects
MH  - White Matter/drug effects/pathology
OTO - NOTNLM
OT  - Aryl hydrocarbon receptor
OT  - Experimental autoimmune encephalomyelitis
OT  - Immunomodulation
OT  - Laquinimod
EDAT- 2016/09/10 06:00
MHDA- 2017/08/18 06:00
CRDT- 2016/09/10 06:00
PHST- 2016/05/05 00:00 [received]
PHST- 2016/06/08 00:00 [accepted]
PHST- 2016/09/10 06:00 [entrez]
PHST- 2016/09/10 06:00 [pubmed]
PHST- 2017/08/18 06:00 [medline]
AID - S0165-5728(16)30135-7 [pii]
AID - 10.1016/j.jneuroim.2016.06.003 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2016 Sep 15;298:9-15. doi: 10.1016/j.jneuroim.2016.06.003. Epub 
      2016 Jun 9.