15-deoxy-Delta(12,14)-prostaglandin J(2) and curcumin modulate the expression of toll-like receptors 4 and 9 in autoimmune T lymphocyte.
BACKGROUND
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Chearwae
Wanida
W
Neuroscience Research Laboratory, Methodist Research Institute at Clarian Health, 1800 North Capitol Avenue, Noyes Building E-504C, Indianapolis, IN 46202, USA.
Bright
John J
JJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D003474:Curcumin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006023:Glycoproteins / Q000008:administration & dosage; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D006023:Glycoproteins; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; C445081:myelin oligodendrocyte glycoprotein (35-55); C435023:myelin proteolipid protein (139-151); D005620:Freund's Adjuvant; D003474:Curcumin; D015230:Prostaglandin D2