TNF-α activated the aggressive phenotypes of RA-HFLSs, including enhanced proliferation, migration, invasion, and inflammation, and inhibited apoptosis. miR-142-3p inhibitor significantly decreased the cell viability, the number of cell clones, the migration rate, the number of invasive cells, the contents and expression of IL-6 and MMP-3, and increased the apoptosis rate and the expressions of Bax and Bad, and decreased Bcl-2 expression of TNF-α-treated RA-HFLSs.
M10 ameliorated arthritis in the CAIA model, and inhibited RANKL, WNT5A, and Bcl-2 expression in RA FLS by blocking IL-6 signaling, likely via Janus kinase-STAT3 pathway downregulation.
Taken together, the key findings of the present study ultimately suggest that GZMB gene silencing acts to inhibit MAPK signaling pathway through regulating the expressions of inflammatory factors, factors correlated with apoptosis (bcl-2 and caspase), as well as factors associated with angiogenesis (VEGF and bFGF), thus relieving synovial tissue hyperplasia and articular cartilage tissue injury brought about by RA.
The combination of si‑Bcl2 and daphnetin exhibited an enhanced effect on rheumatoid arthritis FLS (RAFLS), in which the apoptotic rate was significantly higher than either treatment alone.
Downregulation of miR-20a promoted the expression of STAT3, p-STAT3, and Bcl-2, facilitated FLS cell proliferation, reduced apoptosis and, thereby, played a critical role in RA.
Signal transducer and activator of transcription 3 (STAT3) was identified to be a direct target of miR-29a in RA-FLS. miR-29a overexpression suppressed the expression of STAT3, as well as phosphorylated STAT3(p-STAT3) and its downstream targets protein (Cyclin D1 and Bcl-2).
Knockdown of GREM1 transcripts using short interfering RNA (siRNA) reduced the proliferation and survival of RA-FLS along with downregulation of pErk1/2, pAkt, and Bcl2 expressions, whereas it induced Bax expression.
A small molecule inhibitor of the Bcl-2 family of proteins (ABT-737) restored mitochondrial membrane potential loss and apoptosis in response to cytotoxic agents in 13-cis-RA treated cells.
Consistent with our observations in tumor models, extracellular S100A4 stabilized the p53 tumor suppressor in RA synovial fibroblast-like cells and affected the regulation of p53 target genes, including Bcl-2, p21(WAF), and Hdm-2, as well as matrix metalloproteinases.
This study was undertaken to characterize the expression, regulation, and function of the antiapoptotic Bcl-2 family member Mcl-1 in macrophages isolated from the joints of patients with RA.
We found that blocking IL-15 biological activities using this protein substantially reduced endogenous expression of Bcl-2 and Bcl-x(L), and RA FLS proliferation that was reflected by increased apoptosis.
Fibroblast-like synoviocytes from rheumatoid arthritis patients express functional IL-15 receptor complex: endogenous IL-15 in autocrine fashion enhances cell proliferation and expression of Bcl-x(L) and Bcl-2.
Ad-Rbz-Bcl-2 infection resulted in reduced Bcl-2 expression and cell viability in synovial fibroblasts isolated from RA and osteoarthritis synovial tissues.
To evaluate the clinical impact of this polymorphism, the frequency of bcl-2 polymorphism was investigated in 221 children with insulin-dependent diabetes mellitus (IDDM), 237 adults with autoimmune disease (105 with rheumatoid arthritis, 57 with systemic lupus erythematosus, 55 with Sjögren's syndrome, and 20 others), and 290 healthy Japanese children and adults.
Synovial T cells in rheumatoid arthritis are highly differentiated and express a phenotype suggesting susceptibility to apoptosis (CD45RB dull, CD45RO bright, Bcl-2 low, Bax high, Fas high).
Levels of bcl-2 expression in the lymphocytes of patients with SLE and, for comparison, in the lymphocytes of healthy controls and patients with rheumatoid arthritis (RA), systemic bacterial infections, and chronic B cell lymphocytic leukemia were studied by 2-color cytofluorography and RNA analysis.