Department of Anesthesiology, Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgangxi Road, Hai'zhu District, Guangzhou, 510260, China.
Department of Anesthesiology, Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgangxi Road, Hai'zhu District, Guangzhou, 510260, China.
Neurosci Lett. 2020 Nov 1;738:135356. doi: 10.1016/j.neulet.2020.135356. Epub 2020 Sep 6.
The glucocorticoid receptor (GR) plays a role in inflammatory pain modulation. However, the specific role played by interleukin 6 receptor (IL-6R) in these processes remains elusive. The present study aimed to investigate the extent of inflammation induced by IL-6R and GR.
Male Wistar rats were treated with Freund's complete adjuvant to induce right hind paw inflammation. The levels of IL-6Rα and GR were evaluated in the spinal cord and dorsal root ganglion using Western blot and immunofluorescence assays. Subsequently, we examined the nociceptive behavioral changes following the binding of IL-6R with a GR agonist and/or antagonist, as well as the concentration levels of IL-6 and soluble IL-6R (sIL-6R) in the serum and cerebrospinal fluid. Moreover, the spinal levels of IL-6, IL-6Rα, gp130, JAK2, pJAK2, STAT3, pSTAT3, c-fos, GFAP, and Iba-1 were assessed following anti-IL-6R antibody, sgp130, and dexamethasone intrathecal administration.
Right hind paw inflammation resulted in significant upregulation of IL-6Rα expression in spinal nociceptive neurons, astrocytes, and microglia cells, as well as increased of IL-6Rα and GR colocalization. Notably, anti-IL-6R or dexamethasone attenuated the nociceptive behavior in a dose-dependent manner. Isobologram analysis indicated the sub-additive effects with a concomitant decrease in the spinal levels of IL-6, pJAK2, pSTAT3, c-fos, GFAP, and Iba-1 and increase in the sIL-6R level.
The enhanced mechanical sensitivity accompanying the increase of IL-6Rα and GR was attenuated by anti-IL-6R and dexamethasone application, and the sub-additive effects were regulated by the decreased activation of neurons and glial cells and modulated by IL-6/JAK2/STAT3 signaling pathway, which might be attributed to IL-6 induced trans-signaling.
糖皮质激素受体（GR）在炎症性疼痛调节中发挥作用。然而，白细胞介素 6 受体（IL-6R）在这些过程中所起的具体作用仍不清楚。本研究旨在探讨 IL-6R 和 GR 诱导炎症的程度。
雄性 Wistar 大鼠用完全弗氏佐剂处理以诱导右后爪炎症。使用 Western blot 和免疫荧光测定法评估脊髓和背根神经节中 IL-6Rα 和 GR 的水平。随后，我们研究了 IL-6R 与 GR 激动剂和/或拮抗剂结合后引起的痛觉行为变化，以及血清和脑脊液中 IL-6 和可溶性 IL-6R（sIL-6R）的浓度。此外，在鞘内给予抗 IL-6R 抗体、sgp130 和地塞米松后，评估了脊髓中 IL-6、IL-6Rα、gp130、JAK2、pJAK2、STAT3、pSTAT3、c-fos、GFAP 和 Iba-1 的水平。
右后爪炎症导致脊髓伤害感受神经元、星形胶质细胞和小胶质细胞中 IL-6Rα 表达显著上调，并且 IL-6Rα 和 GR 共定位增加。值得注意的是，抗 IL-6R 或地塞米松以剂量依赖性方式减轻痛觉行为。等辐射分析表明存在亚加和效应，同时脊髓中 IL-6、pJAK2、pSTAT3、c-fos、GFAP 和 Iba-1 的水平降低，sIL-6R 水平升高。
抗 IL-6R 和地塞米松的应用减轻了伴随 IL-6Rα 和 GR 增加的机械敏感性，亚加和效应由神经元和神经胶质细胞的激活减少调节，并通过 IL-6/JAK2/STAT3 信号通路调节，这可能归因于 IL-6 诱导的转信号。
