IL-1β在大鼠颞下颌关节炎性痛中的作用机制探讨

doi:10.19438/j.cjoms.2020.05.004

中国口腔颌面外科杂志 ›› 2020, Vol. 18 ›› Issue (5): 401-406.doi: 10.19438/j.cjoms.2020.05.004

IL-1β在大鼠颞下颌关节炎性痛中的作用机制探讨

潘洪祥, 孙伟, 袁荣涛, 张鹏, 邱建忠

青岛大学附属青岛市市立医院口腔医学中心,山东青岛 266000

收稿日期:2020-04-01 修回日期:2020-06-20 出版日期:2020-09-20 发布日期:2020-10-28
通讯作者: 邱建忠,E-mail：qiujianzhong1969@163.com
作者简介:潘洪祥（1963-）,男,学士,副教授,E-mail：panhongxiang1963@.com
基金资助:
山东省自然科学基金（ZR2016HM34）; 青岛大学附属青岛市市立医院博士科研启动经费（Ⅷ院博201832）

The mechanism of IL-1β contributing to temporomandibular joint inflammatory pain in rats

PAN Hong-xiang, SUN Wei, YUAN Rong-tao, ZHANG Peng, QIU Jian-zhong

Department of Stomatology, Qindao Municipal Hospital Affiliated to Qingdao University. Qingdao266000, Shangdong Province, China

Received:2020-04-01 Revised:2020-06-20 Online:2020-09-20 Published:2020-10-28

摘要/Abstract

摘要： 目的：探讨ERK1/2、NF-κB信号通路是否参与白细胞介素1β（IL-1β）上调疼痛因子Nav1.7的表达,进而参与大鼠颞下颌关节炎性痛。方法：建立颞下颌关节炎症模型或通过大鼠三叉神经节脑立体定位实验,于活体大鼠三叉神经节内注射IL-1β,评估三叉神经节p-ERK1/2、p-p65、Nav1.7、COX-2、p-CREB等分子的表达及摆头阈值变化。体外培养大鼠三叉神经节,IL-1β单独或联合ERK、NF-κB抑制剂U0126、PDTC,利用实时定量 PCR及蛋白免疫印迹评估三叉神经节p-ERK1/2、p-p65、Nav1.7、COX-2、p-CREB的表达变化。采用SPSS 22.0软件包进行数据统计。结果：诱导颞下颌关节炎症24 h及活体大鼠三叉神经节内注射IL-1β 24 h后,三叉神经节内p-ERK1/2、p-p65、Nav1.7、COX-2、p-CREB 表达显著上调,同时摆头阈值降低。ERK及NF-κB抑制剂均可阻断IL-1β上调三叉神经节内Nav1.7、COX-2、p-CREB表达。结论：IL-1β通过ERK1/2、NF-κB信号通路上调三叉神经节内Nav1.7的表达,进而参与大鼠颞下颌关节炎性痛。

关键词: IL-1β, ERK1/2, NF-κB, Nav1.7, 颞下颌关节炎性痛

Abstract: PURPOSE: To investigate whether the ERK1/2 and NF-κB signaling pathways are involved in interleukin-1beta (IL-1β) up-regulation of Nav1.7 expression and then participate in temporomandibular joint (TMJ) inflammatory pain in rats. METHODS: TMJ nociception and the expressions of p-ERK1/2, p-p65, Nav1.7, COX-2, and p-CREB were evaluated after inducing of TMJ inflammation or microinjecting of IL-1β into the trigeminal ganglion (TG). Rats TG explants were treated with IL-1β with or without inhibitors, including U0126 for ERK and PDTC for NF-κB, and then the gene expressions were evaluated using real-time PCR and Western blot assays. Statistical analysis was performed using SPSS 22.0 software package. RESULTS: TMJ inflammation or microinjection of IL-1β into the TG for 24 h both induced TMJ pain and correspondingly up-regulated p-ERK1/2, p-p65, Nav1.7, COX-2, and p-CREB expressions. Both U0126 and PDTC blocked IL-1β up-regulation of Nav1.7, COX-2, p-CREB expressions in TG explants. CONCLUSIONS: IL-1β up-regulates Nav1.7 expression through ERK1/2 and NF-κB signaling pathways, and then contributes to TMJ inflammatory pain in rats.

Key words: IL-1β, ERK1/2, NF-κB, Nav1.7, Temporomandibular inflammatory pain

中图分类号:

R782.6

潘洪祥, 孙伟, 袁荣涛, 张鹏, 邱建忠. IL-1β在大鼠颞下颌关节炎性痛中的作用机制探讨[J]. 中国口腔颌面外科杂志, 2020, 18(5): 401-406.

PAN Hong-xiang, SUN Wei, YUAN Rong-tao, ZHANG Peng, QIU Jian-zhong. The mechanism of IL-1β contributing to temporomandibular joint inflammatory pain in rats[J]. China J Oral Maxillofac Surg, 2020, 18(5): 401-406.

参考文献

[1] 傅开元, 马绪臣, 张震康, 等. 颞下颌关节紊乱综合征关节液IL-6活性及其临床初步探讨[J]. 中华口腔医学杂志, 1995, 30(4): 242-244.
[2] 傅开元, 马绪臣, 张震康, 等. 颞下颌关节紊乱综合征关节液中肿瘤坏死因子活性的检测[J]. 中华口腔医学杂志, 1994, 29(5): 269-271.
[3] 傅开元, 马绪臣, 张震康, 等. 颞下颌关节紊乱综合征关节液白细胞介素1活性及其临床意义[J]. 北京医科大学学报, 1993, 28(6):403-405.
[4] Samad TA, Moore KA, Sapirstein A, et al.Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity[J]. Nature, 2001, 410(6827): 471-475.
[5] Chen X, Han R, Hao P, et al.Nepetin inhibits IL-1beta induced inflammation via NF-kappaB and MAPKs signaling pathways in ARPE-19 cells[J]. Biomed Pharmacother, 2018, 101: 87-93.
[6] Dib-Hajj SD, Black JA, Waxman SG.Voltage-gated sodium channels: therapeutic targets for pain[J]. Pain Med, 2009, 10(7): 1260-1269.
[7] Cox JJ, Reimann F, Nicholas AK, et al.An SCN9A channelopathy causes congenital inability to experience pain[J]. Nature, 2006, 444(7121): 894-898.
[8] Black JA, Liu S, Tanaka M, et al.Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain[J]. Pain, 2004, 108(3): 237-247.
[9] Bi RY, Kou XX, Meng Z, et al.Involvement of trigeminal ganglionic Nav1.7 in hyperalgesia of inflamed temporomandibular joint is dependent on ERK1/2 phosphorylation of glial cells in rats[J]. Eur J Pain, 2013, 17(7): 983-994.
[10] Nassar MA, Stirling LC, Forlani G, et al.Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain[J]. Proc Natl Acad Sci USA, 2004,101(34): 12706-12711.
[11] de Macedo F, Aires RD, Fonseca EG, et al. TNF-α mediated upregulation of NaV1.7 currents in rat dorsal root ganglion neurons is independent of CRMP2 SUMOylation[J]. Mol Brain, 2019, 12(1): 117.
[12] Tamura R, Nemoto T, Maruta T, et al.Up-regulation of NaV1.7 sodium channels expression by tumor necrosis factor-alpha in cultured bovine adrenal chromaffin cells and rat dorsal root ganglion neurons[J]. Anesth Analg, 2014, 118(2): 318-324.
[13] Zhang P, Bi RY, Gan YH.Glial interleukin-1beta upregulates neuronal sodium channel 1.7 in trigeminal ganglion contributing to temporomandibular joint inflammatory hypernociception in rats[J]. J Neuroinflammation, 2018, 15(1): 117.
[14] Huang Y, Zang Y, Zhou L, et al.The role of TNF-alpha/NF-kappa B pathway on the up-regulation of voltage-gated sodium channel Nav1.7 in DRG neurons of rats with diabetic neuropathy[J]. Neurochem Int, 2014, 75:112-119.
[15] Wu YW, Bi RY. Kou XX, et al.17-Beta-estradiol enhanced allodynia of inflammatory temporomandibular joint through upregulation of hippocampal TRPV1 in ovariectomized rats[J]. J Neurosci, 2010, 30(26): 8710-8719.
[16] Zhang P, Gan YH.Prostaglandin E2 upregulated trigeminal ganglionic sodium channel 1.7 involving temporomandibular joint inflammatory pain in rats[J]. Inflammation, 2017, 40(3): 1102-1109.
[17] Lu N, Malemud CJ.Extracellular signal-regulated kinase: a regulator of cell growth, inflammation, chondrocyte and bone cell receptor-mediated gene expression[J]. Int J Mol Sci, 2019, 20(15): 3792-3792.
[18] Stamboulian S, Choi JS, Ahn HS, et al.ERK1/2 mitogen-activated protein kinase phosphorylates sodium channel Na(v)1.7 and alters its gating properties[J]. J Neurosci, 2010, 30(5): 1637-1647.
[19] Zhang Q, Lenardo MJ, Baltimore D.30 years of NF-kappaB: a blossoming of relevance to human pathobiology[J]. Cell, 2017, 168(1-2): 37-57.
[20] Mitchell S, Vargas J, Hoffmann A.Signaling via the NFkappaB system[J]. Wiley Interdiscip Rev Syst Biol Med, 2016, 8(3): 227-241.
[21] Li Z, Li Y, Cao J, et al.Membrane protein Nav1.7 contributes to the persistent post-surgical pain regulated by p-p65 in dorsal root ganglion (DRG) of SMIR rats model[J]. BMC Anesthesiol, 2017, 17(1): 150-150.
[22] Xie MX, Zhang XL, Xu J, et al.Nuclear factor-kappaB gates Nav1.7 channels in DRG neurons via protein-protein interaction[J]. iScience, 2019,19: 623-633.

IL-1β在大鼠颞下颌关节炎性痛中的作用机制探讨

The mechanism of IL-1β contributing to temporomandibular joint inflammatory pain in rats

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 1

编辑推荐

Metrics

本文评价