Department of Geriatric Cardiology, Xiangya Hospital,Central South University, Changsha, 410008, China.
Int Immunopharmacol. 2011 Dec;11(12):2118-24. doi: 10.1016/j.intimp.2011.09.005. Epub 2011 Sep 29.
Toll-like receptor 3 (TLR3), a member of the TLR family that recognizes double-stranded RNA (dsRNA), plays an important role in antiviral immunity. TLR3 is widely expressed in various cells and the activation of TLR3 induces cell apoptosis in some cells. However, the effect of TLR3 on cell proliferation in endothelial progenitor cells (EPCs) is unclear. In this study, we found that EPCs expressed high levels of TLR1, 3, 4, and 6 and low levels of TLR2, 5, 7, 8, and 10. The treatment of EPCs with TLR3 agonist Poly I:C up-regulated the expression of cytokines IL-1β, IL-6, IL-8, TNF-α, IFN-α, and IFN-β, indicating that EPCs expressed functional TLR3. Moreover, Poly I:C treatment induced cell cycle progress inhibition and cell apoptosis, leading to the inhibition of cell proliferation. Further studies indicated that IL-1β was involved in TLR3-induced cell proliferation inhibition, as IL-1β inhibited cell proliferation in a dose-dependent manner, and the IL-1β receptor type I (IL-1R1)-neutralizing antibody ameliorated Poly I:C-induced cell proliferation inhibition. Taken together, these results suggest that Poly I:C impairs cell proliferation by inducing cell cycle progress inhibition and cell apoptosis via TLR3 in EPCs.
Toll 样受体 3（TLR3）是识别双链 RNA（dsRNA）的 TLR 家族成员，在抗病毒免疫中发挥重要作用。TLR3 在各种细胞中广泛表达，激活 TLR3 可诱导某些细胞发生细胞凋亡。然而，TLR3 对内皮祖细胞（EPCs）中细胞增殖的影响尚不清楚。在本研究中，我们发现 EPCs 表达高水平的 TLR1、3、4 和 6，低水平的 TLR2、5、7、8 和 10。TLR3 激动剂 Poly I:C 处理 EPCs 可上调细胞因子 IL-1β、IL-6、IL-8、TNF-α、IFN-α 和 IFN-β 的表达，表明 EPCs 表达功能性 TLR3。此外，Poly I:C 处理诱导细胞周期进展抑制和细胞凋亡，从而抑制细胞增殖。进一步的研究表明，IL-1β 参与了 TLR3 诱导的细胞增殖抑制，因为 IL-1β 呈剂量依赖性抑制细胞增殖，而 IL-1β 受体 I 型（IL-1R1）中和抗体可改善 Poly I:C 诱导的细胞增殖抑制。综上所述，这些结果表明 Poly I:C 通过 TLR3 在 EPCs 中诱导细胞周期进展抑制和细胞凋亡来损害细胞增殖。
