Downregulation of IL-17 and IL-6 in the central nervous system by glatiramer acetate in experimental autoimmune encephalomyelitis.
T helper 17 (Th17) cells are pivotal in the immune pathogenesis of EAE. Glatiramer acetate (GA) can enhance Treg FOXp3 expression. We demonstrate that GA downregulates the expression of both IL-17 and IL-6 in two different EAE models. Increased mRNA expression in CNS for ROR gamma t, IL-17, IL-12/IL-23, IL-6, TNF-alpha, STAT4 and Th1 cytokines were significantly reduced by GA with a concomitant rise in SMAD3. The increased expression of TNF-alpha, IL-6, and IL-17 in CNS of CD25+ depleted animals was suppressed by GA treatment. This study demonstrates that both Th1 polarization and Th17 expression are modulated by GA.
Begum-Haque
Sakhina
S
Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA. Sakhina.Haque-Begum@Dartmouth.EDU
Sharma
Alok
A
Kasper
Isaac R
IR
Foureau
David M
DM
Mielcarz
Daniel W
DW
Haque
Azizul
A
Kasper
Lloyd H
LH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D002490:Central Nervous System / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000068717:Glatiramer Acetate; D006023:Glycoproteins; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism
D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D015850:Interleukin-6; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D050797:STAT4 Transcription Factor; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C494091:Stat4 protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55); D000068717:Glatiramer Acetate