Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
CD4-Positive T-Lymphocytes / pathology
-
Central Nervous System / drug effects*
-
Cytokines / metabolism
-
Disease Models, Animal
-
Down-Regulation / drug effects*
-
Down-Regulation / genetics
-
Encephalomyelitis, Autoimmune, Experimental / chemically induced
-
Encephalomyelitis, Autoimmune, Experimental / genetics
-
Encephalomyelitis, Autoimmune, Experimental / pathology*
-
Encephalomyelitis, Autoimmune, Experimental / prevention & control
-
Female
-
Forkhead Transcription Factors / metabolism
-
Glatiramer Acetate
-
Glycoproteins
-
Immunosuppressive Agents / pharmacology*
-
Immunosuppressive Agents / therapeutic use
-
Interleukin-17 / genetics
-
Interleukin-17 / metabolism*
-
Interleukin-6 / genetics
-
Interleukin-6 / metabolism*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments
-
Peptides / pharmacology*
-
Peptides / therapeutic use
-
RNA, Messenger / metabolism
-
Receptors, Antigen, T-Cell / genetics
-
STAT4 Transcription Factor / metabolism
-
Smad3 Protein / metabolism
Substances
-
Cytokines
-
Forkhead Transcription Factors
-
Foxp3 protein, mouse
-
Glycoproteins
-
Immunosuppressive Agents
-
Interleukin-17
-
Interleukin-6
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments
-
Peptides
-
RNA, Messenger
-
Receptors, Antigen, T-Cell
-
STAT4 Transcription Factor
-
Smad3 Protein
-
Smad3 protein, mouse
-
Stat4 protein, mouse
-
myelin oligodendrocyte glycoprotein (35-55)
-
Glatiramer Acetate