Retracted: CCR5 silencing reduces inflammatory response, inhibits viability, and promotes apoptosis of synovial cells in rat models of rheumatoid arthritis through the MAPK signaling pathway

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that can, in severe cases, lead to disability. CC chemokine receptor (CCR), an integral membrane protein, has been suggested to play a key role in the RA developmentThis study is to explore the role of CCR5 silencing in inflammatory response, viability, and apoptosis of synovial cells in RA rats by inactivating the mitogen‐activated protein kinase (MAPK) signaling pathway. Microarray analysis was conducted to screen out differentially expressed genes from RA‐related chips. The rat model was established by injection of siRNA‐CCR5 and PD98059 (inhibitor of mitogen‐activated protein kinase kinase 1) to evaluate the role of CCR5 silencing in RA, with the involvement of inflammatory response, synovial cell viability, apoptosis, and cycle. CCR5 was predicted to participate in RA by regulating the MARK pathway. In animal experiments, reduction was identified in arthritis index (AI), CCR5 positive expression rate, levels of tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), matrix metalloproteinase (MMP)‐1, and MMP‐3 in serum of RA rats after CCR5 siRNA and PD98059 injections. RA rats treated with CCR5 siRNA, and PD98059 presented with inhibition in cell viability, promotion of apoptosis, increase in cell proportion in G0/G1 phase, and shortened the S phase. In addition, the treatment of CCR5 siRNA, and PD98059 resulted in downregulated JNK1, ERK1, p38, Cyclin D1, Cyclin E1, Cyclin B1, and Bcl‐2 and upregulated Bax and Cas3. These findings reveal that CCR5 silencing suppresses inflammatory response, inhibits viability, and promotes apoptosis of synovial cells in RA rats by inhibiting MAPK pathway. Therefore, CCR5 silencing may provide a novel therapeutic target for RA.

C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload

“…Studies have shown that in drug-induced liver injury, CCR5 activates M1 polarization and prevents M2 polarization via the MAPK pathway (51,52). Another study demonstrated that CCR5 silencing inhibits the inflammatory response in rheumatoid arthritis rats by inhibiting the MAPK pathway, and also inhibits viability and promotes synoviocyte apoptosis (53). Ang II has been shown to promote cardiac tissue growth and contribute to pressure overload-induced cardiac hypertrophy (54,55).…”

C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis

“…The infiltration of such IFN-γ secreting CCR5 + CD4+ T cells into the RA joint cavity is regulated by the synovial microenvironment [28]. On the other hand, CCR5 silencing suppresses inflammatory response in RA by inhibiting synovial cell viability but promoting apoptosis [29]. Another source of CCR5 in RA are Vδ2 T cells which infiltrated into the synovium under the influence of high levels of TNF-α [30].…”

C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis, and Hydroxychloroquine: In silico analysis 

“…The in ltration of such IFN-γ secreting CCR5+CD4+ T cells into the RA joint cavity is regulated by the synovial microenvironment [29]. On the other hand, CCR5 silencing suppresses in ammatory response in RA by inhibiting synovial cell viability but promoting apoptosis [30]. Another source of CCR5 in RA are Vδ2 T cells which in ltrated into the synovium under the in uence of high levels of TNF-α [31].…”