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

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, n = 20 ), OA ( n = 25 ), and RA (n =49) patients were compared via ELISA. The different expression levels of AIM2, ASC, caspase-1, and IL-1β between RA and OA synovium were semiquantified by qRT-PCR and immunohistochemical (IHC) staining. IHC staining was recorded by H 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-1β 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-1β were expressed higher in RA than that of OA. Moreover, the H scores of AIM2, ASC, and IL-1β 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.

Cell-Free DNA in Rheumatoid Arthritis

“…The H scores, a semiquantitative immunohistochemical parameter [88], for AIM2 and IL-1β correlated with ESR and CRP levels in patients with RA. Moreover, RNA silencing of AIM2 expression inhibited FLS proliferation [89]. Thus, the AIM2 inflammasome pathway in FLS may be involved in the pathogenesis of RA and may be a therapeutic target.…”

Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy

“… 20 On the contrary, an independent study reported high soluble levels of ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1, and IL-1β in OA patients compared with healthy blood donors; however, its consequence on OA phenotype was not discussed. 48 Soluble factors associated with inflammasome activation have also been observed locally. Synovial fluid from temporomandibular OA patients showed high concentrations of NLRP3, caspase-1, IL-1β, and IL-18, suggesting these molecules initiate degenerative processes in situ.…”

Myricitrin inhibits fibroblast-like synoviocyte-mediated rheumatoid synovial inflammation and joint destruction by targeting AIM2

“…More importantly, it was reported that AIM2 was increased in RA synovium compared to osteoarthritis (OA) patients. In addition, AIM2 knockdown suppresses the proliferation of RA FLSs but not cell migration and apoptosis ( Chen et al, 2020 ). Herein, we observed some different results.…”