The immunomodulatory effect of laquinimod in CNS autoimmunity is mediated by the aryl hydrocarbon receptor

Autor: Ralf Gold, Megan G. Massa, Charlotte Esser, Jan Thöne, Johannes Berg, Aiden Haghikia, Yasaman Mahmoudjanlou, Alexander Duscha
Rok vydání: 2016
Předmět:
0301 basic medicine
CD3 Complex
T-Lymphocytes
Immunology
Demyelinating Autoimmune Diseases
CNS
Quinolones
Neuroprotection
Myelin oligodendrocyte glycoprotein
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Leukemic Infiltration
Neurotrophic factors
medicine
Animals
Immunologic Factors
Immunology and Allergy
RNA
Messenger
Mice
Knockout
Brain-derived neurotrophic factor
Analysis of Variance
biology
Brain-Derived Neurotrophic Factor
Multiple sclerosis
Experimental autoimmune encephalomyelitis
Aryl hydrocarbon receptor
medicine.disease
White Matter
Axons
Peptide Fragments
Rats
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Gene Expression Regulation
Receptors
Aryl Hydrocarbon
Spinal Cord
Neurology
chemistry
biology.protein
Myelin-Oligodendrocyte Glycoprotein
Neurology (clinical)
Laquinimod
030217 neurology & neurosurgery
Zdroj: Journal of Neuroimmunology. 298:9-15
ISSN: 0165-5728
DOI: 10.1016/j.jneuroim.2016.06.003
Popis: 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.
Databáze: OpenAIRE
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