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Peripheral soluble epoxide hydrolase inhibition reduces hypernociception and inflammation in albumin-induced arthritis in temporomandibular joint of rats.
International Immunopharmacology ( IF 4.8 ) Pub Date : 2020-07-28 , DOI: 10.1016/j.intimp.2020.106841
Juliana Maia Teixeira 1 , Henrique Ballassini Abdalla 1 , Rosanna Tarkany Basting 1 , Bruce D Hammock 2 , Marcelo Henrique Napimoga 1 , Juliana Trindade Clemente-Napimoga 1
Affiliation  

Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial tissue, joint dysfunction, and damage. Epoxyeicosatrienoic acids (EETs) are endogenous anti-inflammatory compounds, which are quickly converted by the soluble epoxide hydrolase (sEH) enzyme into a less active form with decreased biological effects. The inhibition of the sEH enzyme has been used as a strategy to lower nociception and inflammation. The goal of this study was to investigate whether the peripheral treatment with the sEH enzyme inhibitor 1- trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) could prevent the hypernociception and inflammation in the albumin-induced arthritis model in rats’ temporomandibular joint (TMJ). After the induction of experimental arthritis, animals were assessed for nociceptive behavior test, leukocyte infiltration counts and histologic analysis, ELISA to quantify several cytokines and Western blotting. The peripheral pretreatment with TPPU inhibited the arthritis-induced TMJ hypernociception and leukocyte migration. Moreover, the local concentrations of proinflammatory cytokines were diminished by TPPU, while the anti-inflammatory cytokine interleukin-10 was up-regulated in the TMJ tissue. Finally, TPPU significantly decreased protein expression of iNOS, while did not alter the expression of MRC1. This study provides evidence that the peripheral administration of TPPU reduces hypernociception and inflammation in TMJ experimental arthritis.



中文翻译:

外周可溶性环氧化物水解酶抑制可减少大鼠颞下颌关节白蛋白诱导的关节炎的过度伤害感受和炎症。

类风湿性关节炎 (RA) 的特征是滑膜组织的慢性炎症、关节功能障碍和损伤。环氧二十碳三烯酸 (EET) 是内源性抗炎化合物,可通过可溶性环氧化物水解酶 (sEH) 快速转化为活性较低的形式,生物效应降低。sEH 酶的抑制已被用作降低伤害感受和炎症的策略。本研究的目的是调查用 sEH 酶抑制剂 1-三氟甲氧基苯基-3-(1-丙酰基哌啶-4-基) 脲 (TPPU) 进行外周治疗是否可以预防白蛋白诱导的关节炎模型中的过度伤害感受和炎症。大鼠的颞下颌关节 (TMJ)。实验性关节炎诱导后,对动物进行伤害性行为测试,白细胞浸润计数和组织学分析,ELISA 量化几种细胞因子和蛋白质印迹。用 TPPU 进行外周预处理可抑制关节炎引起的 TMJ 过度伤害感受和白细胞迁移。此外,TPPU 降低了局部促炎细胞因子的浓度,而 TMJ 组织中的抗炎细胞因子白细胞介素 10 上调。最后,TPPU 显着降低 iNOS 的蛋白表达,而没有改变 MRC1 的表达。这项研究提供了证据,证明外周给药 TPPU 可减少 TMJ 实验性关节炎的过度伤害感受和炎症。用 TPPU 进行外周预处理可抑制关节炎引起的 TMJ 过度伤害感受和白细胞迁移。此外,TPPU 降低了局部促炎细胞因子的浓度,而 TMJ 组织中的抗炎细胞因子白细胞介素 10 上调。最后,TPPU 显着降低 iNOS 的蛋白表达,而没有改变 MRC1 的表达。这项研究提供了证据,证明外周给药 TPPU 可减少 TMJ 实验性关节炎的过度伤害感受和炎症。用 TPPU 进行外周预处理可抑制关节炎引起的 TMJ 过度伤害感受和白细胞迁移。此外,TPPU 降低了局部促炎细胞因子的浓度,而 TMJ 组织中的抗炎细胞因子白细胞介素 10 上调。最后,TPPU 显着降低 iNOS 的蛋白表达,而没有改变 MRC1 的表达。这项研究提供了证据,证明外周给药 TPPU 可减少 TMJ 实验性关节炎的过度伤害感受和炎症。

更新日期:2020-07-28
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