MicroRNA-21 (miR-21) is overexpressed in patients with rheumatoid arthritis (RA). This study was designed to investigate the effect and mechanism of miR-21 on cell proliferation in fibroblast-like synoviocytes (FLS) of RA. FLS were primary-cultured from a rat RA model. RA-FLS and normal FLS were infected with lentivirus (anti-miR-21 or pro-miR-21) for overexpression or downregulation of miR-21, respectively. The effects of miR-21 overexpression or inhibition on nucleoprotein NF-κB levels and FLS cell proliferation were evaluated by western blotting and MTT assays. The effects of an inhibitor of NF-κB nuclear translocation (BAY 11-7082) were also evaluated. The results showed that the levels of miR-21 and nucleoprotein NF-κB were increased in FLS of RA model rats compared to the control group. Downregulation of miR-21 in RA FLS led to a significant decrease in nucleoprotein NF-κB levels and cell proliferation rates compared to the antinegative control (NC) group. However, miR-21 overexpression in normal FLS resulted in a significant increase of nucleoprotein NF-κB levels and cell proliferation rates compared to the pro-NC group. The effects of miR-21 overexpression were reversed by BAY 11-7082. We concluded that upregulated miR-21 in FLS in RA model rats may promote cell proliferation by facilitating NF-κB nuclear translocation, thus affecting the NF-κB pathway.

Background. Antitumor necrosis factor (anti-TNF) drugs have been applied for rheumatoid arthritis (RA) treatment; however, patients having anti-drug antibodies (ADAbs) do not benefit from these drugs. The meta-analysis aims to comprehensively assess the relationship between ADAb positive (ADAb+) and anti-TNF response in RA patients. Methods. Observational studies comparing different clinical response between ADAb+ and ADAb negative groups were included. Odds ratio (OR) with its corresponding 95% confidence interval (CI) was used as effect size. Subgroup analyses stratified by TNF inhibitor types and assay methods for ADAb detection were performed. Results. Totally, 10 eligible studies containing 1806 subjects were included. ADAb+ was significantly associated with reduced anti-TNF response to RA at all the time points after follow-up (P < 0.001). Subgroup analysis also supported this significant association (P < 0.05), except for enzyme-linked immunosorbent assay (ELISA) group at 3 months, infliximab (INF) and enzyme-linked immunosorbent assay (ELISA) groups at 6 months, and Immunological Multi-Parameter Chip Technology (IMPACT) group at 12 months. Conclusion. ADAb+ was significantly associated with reduced clinical response in RA patients, and other alternatives should be considered in RA patients presenting ADAb+.

Objective: Metastatic breast cancer-induced bone cancer pain (BCP) is one of the most disabling factors in patients suffering. Recent studies show thymic stromal lymphopoietin (TSLP) is a proinflammatory factor and high expression in cancer cells. Here we investigated whether and how TSLP released form breast cancer cells contributes to BCP. Methods: Braset cancer cells MDA-MB-231 were intramedullary injected into the femur to induce BCP, TSLP neutralizing antibody was intrathecally injected and pain hypersensitivity was checked by behavioral testing. The TSLP expression was knockdown by shRNA. Human TSLP, TNF-α, IL-1β, IL-6, CCL2, CXCL2 and CXCL5 in intramedullary space of the femur of rats was detected by ELISA. Results: TSLP neutralizing antibody intrathecally injection significantly reduced MDA-MB-231 cells inoculation induced persistent mechanical allodynia and heat hyperalgesia and TSLP increased. Furthermore, Persistent mechanical allodynia and heat hyperalgesia of mice models were also decreased in MDA-MB-231 cells with TSLP knockdown. Finally, some inflammatory factors, TNF-α, IL-1β, IL-6, CCL2, CXCL2 and CXCL5 were significantly elevated in the intramedullary space lavage fluid of the right femur after cancer cell inoculation, but were obviously reduced in models with neutralizing antibody of TSLP treatment and TSLP knockdown. Conclusion: TSLP-mediated inflammatory factors release contributes to the maintenance of tumoral hypersensitivity. Inhibition of the TSLP may provide a new therapy for BCP management.