Journal of Clinical Immunology

, Volume 28, Issue 5, pp 558–570 | Cite as

15-Deoxy-Δ12,14-Prostaglandin J2 and Curcumin Modulate the Expression of Toll-like Receptors 4 and 9 in Autoimmune T Lymphocyte

Article

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-Δ12,14-prostaglandin J2 (15d-PGJ2) 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-PGJ2 and curcumin suggests new therapeutic targets in the treatment of T cell-mediated autoimmune diseases.

Keywords

Autoimmune disease EAE/MS inflammation Th1 cell toll-like receptor 

Abbreviations

MS

multiple sclerosis

EAE

experimental allergic encephalomyelitis

MBP

myelin basic protein

MOG

myelin oligodendrocyte glycoprotein

PLP

proteolipid protein

CNS

central nervous system

PPARγ

peroxisome proliferator-activated receptor gamma

15d-PGJ2

15-deoxy-Δ12,14-prostaglandin J2

TZD

thiazolidinediones

APC

antigen-presenting cells

Th1

T helper 1

PAMP

pathogen-associated molecular patterns

LPS

lipopolysaccharide

IRAK

interleukin 1 receptor-associated kinase

TRAF

tumor necrosis factor receptor-associated factor

NF-κB

nuclear factor kappa B

AP-1

activated protein 1

MAPK

mitogen-activated protein kinase

MHC, major histocompatibility complex

PE, phycoerythrin

FITC

fluorescence isothiocyanate

FBS

fetal bovine serum

BSA

bovine serum albumin

CFA

complete Freund’s adjuvant

DMSA

dimethylesulfoxide

MCS

mean clinical score

Notes

Acknowledgments

This work was supported in part by the National Institutes of Health, grant R01 NS42257-01A1 (to J.J.B).

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© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Neuroscience Research LaboratoryMethodist Research Institute at Clarian HealthIndianapolisUSA
  2. 2.Department of MedicineIndiana University School of MedicineIndianapolisUSA

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