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AIM2 在类风湿关节炎中的表达及其对成纤维样滑膜细胞的作用。

Expression of AIM2 in Rheumatoid Arthritis and Its Role on Fibroblast-Like Synoviocytes.

机构信息

Rheumatology Department, Integrated Traditional Chinese and Western Medicine Hospital, Southern Medical University, Guangzhou 510315, China.

出版信息

Mediators Inflamm. 2020 Oct 26;2020:1693730. doi: 10.1155/2020/1693730. eCollection 2020.

Abstract

OBJECTIVES

To determine differences in AIM2 inflammasome expression levels between rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate the role of AIM2 in RA fibroblast-like synoviocytes (RA-FLS).

METHODS

Serum AIM2 levels among health controls (HC, = 20), OA ( = 25), and RA ( =49) patients were compared via ELISA. The different expression levels of AIM2, ASC, caspase-1, and IL-1 between RA and OA synovium were semiquantified by qRT-PCR and immunohistochemical (IHC) staining. IHC staining was recorded by scores, and its correlation with the ESR and CRP levels of RA patients was determined. SiRNA AIM2 was transferred to RA-FLS and its effects on the proliferation and migration via CCK-8 assay and Transwell test, respectively.

RESULTS

In RA sera, the HC expressed higher level of AIM2 than OA and RA patients, and ASC, caspase-1, and IL-1 expressed higher in RA patients than HC; no significant differences were observed between sera of OA and RA patients. However, in affected knee synovium, AIM2, ASC, caspase-1, and IL-1 were expressed higher in RA than that of OA. Moreover, the scores of AIM2, ASC, and IL-1 were positively correlated with the ESR and CRP levels in RA patients. The proliferation of FLS was significantly inhibited after transferring with AIM2 siRNA to FLS. There were no differences in apoptosis and migration assay between the si-AIM2 group and the control group.

CONCLUSION

AIM2 inflammasome pathway involves in the pathogenesis of RA. si-AIM2 inhibits the proliferation of RA-FLS, which may be a promising therapeutic strategy for the treatment of RA.

摘要

目的

比较关节炎(RA)和骨关节炎(OA)患者中 AIM2 炎症小体的表达水平差异,并探讨 AIM2 在 RA 成纤维样滑膜细胞(RA-FLS)中的作用。

方法

通过 ELISA 比较健康对照组(HC,n=20)、OA(n=25)和 RA(n=49)患者血清中的 AIM2 水平。通过 qRT-PCR 和免疫组化(IHC)染色半定量检测 RA 和 OA 滑膜中 AIM2、ASC、caspase-1 和 IL-1 的不同表达水平。通过 评分记录 IHC 染色,并确定其与 RA 患者 ESR 和 CRP 水平的相关性。将 siRNA AIM2 转染至 RA-FLS,通过 CCK-8 检测和 Transwell 试验分别检测其对细胞增殖和迁移的影响。

结果

在 RA 血清中,HC 表达的 AIM2 水平高于 OA 和 RA 患者,且 RA 患者 ASC、caspase-1 和 IL-1 的表达水平高于 HC;OA 和 RA 患者的血清中未观察到明显差异。然而,在受影响的膝关节滑膜中,RA 患者的 AIM2、ASC、caspase-1 和 IL-1 的表达水平高于 OA。此外,RA 患者 AIM2、ASC 和 IL-1 的 评分与 ESR 和 CRP 水平呈正相关。将 AIM2 siRNA 转染至 FLS 后,FLS 的增殖明显受到抑制。si-AIM2 组与对照组之间在凋亡和迁移试验中没有差异。

结论

AIM2 炎症小体途径参与 RA 的发病机制。si-AIM2 抑制 RA-FLS 的增殖,可能是治疗 RA 的一种有前途的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46a1/7605934/4558193e9efb/MI2020-1693730.001.jpg

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