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在关节炎不同阶段大鼠痛觉过敏变化的行为和细胞方面,血清 IL10 水平与 p38MAPK 酶活性的关系。

Relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects of variation of hyperalgesia during different stages of arthritis in rats.

机构信息

Physiology Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran,

出版信息

Inflammopharmacology. 2014 Feb;22(1):37-44. doi: 10.1007/s10787-013-0174-8. Epub 2013 Jun 14.

Abstract

OBJECTS AND DESIGN

Regarding to anti-inflammatory role of interleukin (IL) 10, its inhibitory effects on p38MAPK activity and, different pro and anti-inflammatory roles of activated p38MAPK in cells, this study was aimed to investigate relationship between serum IL10 level and p38MAPK enzyme activity on behavioral and cellular aspects variation of hyperalgesia during different stages of arthritis in rats.

MATERIALS AND METHODS

Adjuvant arthritis (AA) was induced by a single subcutaneous injection of complete Freund's adjuvant into the rats' hind paw. Behavioral and inflammatory responses were assessed at 0, 3, 7, 14, and 21 days of study. Receptor and other protein enzyme expression variations were detected by western blotting. Anti-IL10 and p38MAPK inhibitor were administered daily during the 21 days of study.

RESULT

Daily treatment with anti-IL10 antibody significantly increased paw edema and hyperalgesia in the AA group compared with the AA control group. Administration of anti-IL10 antibody caused significant increase in the ratio of phosphorylated p38 to p38MAPK enzyme level expression on 14th and 21st days of study compared with the AA control group.

CONCLUSION

Our study confirmed that a part of anti- inflammatory effects of serum IL10 during AA inflammation was mediated via inhibition of p38MAPK enzyme phosphorylation. Moreover, these findings suggest that increase in the level of spinal mu opioid receptor expression during AA inflammation is not mediated via the direct effect of serum IL10 on spinal p38MAPK.

摘要

目的

鉴于白细胞介素(IL)10 具有抗炎作用,其可抑制 p38MAPK 活性,且激活的 p38MAPK 在细胞中具有不同的促炎和抗炎作用,本研究旨在探讨血清 IL10 水平与 p38MAPK 酶活性在大鼠关节炎不同阶段痛觉过敏的行为和细胞变化方面的关系。

材料和方法

通过向大鼠后足皮下注射完全弗氏佐剂诱导佐剂性关节炎(AA)。在研究的第 0、3、7、14 和 21 天评估行为和炎症反应。通过 Western 印迹检测受体和其他蛋白酶表达的变化。在 21 天的研究期间,每天给予抗 IL10 抗体和 p38MAPK 抑制剂治疗。

结果

与 AA 对照组相比,每日给予抗 IL10 抗体治疗显著增加 AA 组的爪肿胀和痛觉过敏。与 AA 对照组相比,在研究的第 14 天和第 21 天,给予抗 IL10 抗体后,磷酸化 p38 与 p38MAPK 酶水平表达的比值显著增加。

结论

我们的研究证实,血清 IL10 在 AA 炎症过程中的部分抗炎作用是通过抑制 p38MAPK 酶磷酸化介导的。此外,这些发现表明,AA 炎症过程中脊髓 μ 阿片受体表达水平的增加不是通过血清 IL10 对脊髓 p38MAPK 的直接作用介导的。

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