Abstract
Introduction:
Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease model for multiple sclerosis (MS). We have shown earlier that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and curcumin ameliorate EAE by modulating inflammatory signaling pathways in T lymphocytes. Toll-like receptors (TLRs), expressed primarily in innate immune cells, play critical roles in the pathogenesis of EAE. T lymphocytes also express TLRs and function as costimulatory receptors to upregulate proliferation and cytokine production in response to specific agonists.
Discussion:
In this study, we show that naïve CD4(+) and CD8(+) T cells express detectable levels of TLR4 and TLR9 and that increase after the induction of EAE in SJL/J and C57BL/6 mice by immunization with PLPp139-151 and MOGp35-55 antigen, respectively. It is interesting to note that in vivo treatment with 15d-PGJ2 or curcumin results in a significant decrease in TLR4 and TLR9 expression in CD4(+) and CD8(+) T cells in association with the amelioration of EAE.
Conclusion:
Although the exact mechanisms are not known, the modulation of TLR expression in T lymphocytes by 15d-PGJ(2) and curcumin suggests new therapeutic targets in the treatment of T cell-mediated autoimmune diseases.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism*
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Curcumin / administration & dosage*
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Disease Models, Animal
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Female
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Freund's Adjuvant / administration & dosage
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Glycoproteins / administration & dosage
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Humans
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Immunization
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Mice
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Mice, Inbred C57BL
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Multiple Sclerosis / drug therapy*
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Multiple Sclerosis / immunology
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Myelin Proteolipid Protein / administration & dosage
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / administration & dosage
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Prostaglandin D2 / administration & dosage
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Prostaglandin D2 / analogs & derivatives*
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / immunology
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Toll-Like Receptor 4 / metabolism*
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Toll-Like Receptor 9 / genetics
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Toll-Like Receptor 9 / immunology
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Toll-Like Receptor 9 / metabolism*
Substances
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15-deoxy-delta(12,14)-prostaglandin J2
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Glycoproteins
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Myelin Proteolipid Protein
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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Toll-Like Receptor 4
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Toll-Like Receptor 9
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myelin oligodendrocyte glycoprotein (35-55)
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myelin proteolipid protein (139-151)
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Freund's Adjuvant
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Curcumin
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Prostaglandin D2