Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat.
Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat.
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DOI：
10.1186/1744-8069-7-15
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发表时间：
2011-02-22
期刊：
影响因子：
3.3
通讯作者：
Tao KS
中科院分区：
文献类型：
--
作者：
Qian NS;Liao YH;Feng QX;Tang Y;Dou KF;Tao KS
慢性胰腺炎（CP）疼痛的潜在机制尚未完全了解。我们以前的数据表明，星形胶质细胞积极参与。然而，尚不清楚CP条件下星形胶质细胞活化是如何诱导的。在本研究中，我们假设Toll样受体（TLR）参与了CP诱导的疼痛中星形胶质细胞的激活和疼痛行为。为了验证我们的假设，我们首先研究了三硝基苯磺酸（TNBS）胰腺内灌注诱导的大鼠CP模型中TLR 2 -4的变化。Western blot结果显示，TNBS刺激后，TLR 3逐渐升高，并维持在较高水平达5 w，而TLR 2和TLR 4则无明显变化，且与机械性痛觉超敏的病程变化相关。双重免疫染色表明TLR 3在星形胶质细胞上高度表达。输注TLR 3反义寡核苷酸（阿索）剂量依赖性地减弱CP诱导的异常性疼痛。CP诱导的脊髓星形胶质细胞活化也被TLR 3阿索显著抑制。实时荧光定量PCR检测结果显示，胰腺炎大鼠脊髓中IL-1β、TNF-α、IL-6和单核细胞趋化蛋白-1（MCP-1）的表达均显著升高。此外，TLR 3阿索显著减弱CP诱导的IL-1β和MCP-1的上调。这些结果表明，在CP条件下，脊髓背角中可能存在“TLR 3-星形胶质细胞-IL-1β/MCP-1”通路作为正反馈回路。TLR 3介导的神经免疫相互作用可能是治疗CP患者持续性疼痛的新靶点。
Mechanisms underlying pain in chronic pancreatitis (CP) are incompletely understood. Our previous data showed that astrocytes were actively involved. However, it was unclear how astrocytic activation was induced in CP conditions. In the present study, we hypothesized that toll-like receptors (TLRs) were involved in astrocytic activation and pain behavior in CP-induced pain. To test our hypothesis, we first investigated the changes of TLR2-4 in the rat CP model induced by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). Western blot showed that after TNBS infusion, TLR3, but not TLR2 or TLR4, was increased gradually and maintained at a very high level for up to 5 w, which correlated with the changing course of mechanical allodynia. Double immunostaining suggested that TLR3 was highly expressed on astrocytes. Infusion with TLR3 antisense oligodeoxynucleotide (ASO) dose-dependently attenuated CP-induced allodynia. CP-induced astrocytic activation in the spinal cord was also significantly suppressed by TLR3 ASO. Furthermore, real-time PCR showed that IL-1β, TNF-α, IL-6 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in spinal cord of pancreatic rats. In addition, TLR3 ASO significantly attenuated CP-induced up-regulation of IL-1β and MCP-1. These results suggest a probable "TLR3-astrocytes-IL-1β/MCP-1" pathway as a positive feedback loop in the spinal dorsal horn in CP conditions. TLR3-mediated neuroimmune interactions could be new targets for treating persistent pain in CP patients.
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影响因子：
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