15-deoxy-Δ12,14-prostaglandin J2 and curcumin modulate the expression of toll-like receptors 4 and 9 in autoimmune T lymphocyte
15-deoxy-Δ12,14-prostaglandin J2 and curcumin modulate the expression of toll-like receptors 4 and 9 in autoimmune T lymphocyte
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DOI：
10.1007/s10875-008-9202-7
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发表时间：
2008-09-01
影响因子：
9.1
通讯作者：
Bright, John J.
中科院分区：
文献类型：
--
作者：
Chearwae, Wanida;Bright, John J.
实验性过敏性脑脊髓炎（EAE）是一种T细胞介导的多发性硬化症（MS）自身免疫性疾病模型。我们之前已经证明15-脱氧- δ(12,14)-前列腺素J(2) （15d- PGJ(2)）和姜黄素通过调节T淋巴细胞中的炎症信号通路来改善EAE。toll样受体（TLRs）主要在先天免疫细胞中表达，在EAE的发病机制中起关键作用。T淋巴细胞也表达TLRs，并作为共刺激受体，在特定激动剂的作用下上调增殖和细胞因子的产生。在本研究中，我们发现，分别用PLPp139-151和MOGp35-55抗原免疫SJL/J和C57BL/6小鼠，初始CD4+和CD8(+) T细胞表达可检测水平的TLR4和TLR9，并在诱导EAE后增加。有趣的是，体内用15d-PGJ2或姜黄素治疗可导致CD4（+）和CD8(+) T细胞中TLR4和TLR9表达显著降低，这与EAE的改善有关。结论虽然确切的机制尚不清楚，但15d-PGJ(2)和姜黄素对T淋巴细胞中TLR表达的调节为治疗T细胞介导的自身免疫性疾病提供了新的治疗靶点。
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 naive 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.