类风湿性关节炎（RA）是一种由自身免疫反应介导的慢性炎症。据报道，杆状病毒 IAP 重复序列 2 (BIRC2) 和肿瘤坏死因子受体 1 相关死亡域蛋白 (TRADD) 在 RA 中高表达，但它们在 RA 进展过程中的具体作用仍不清楚。本研究旨在探讨BIRC2/TRADD在RA进展过程中的特异性调控。通过脂多糖（LPS）刺激C28/I2细胞建立体外RA细胞模型。通过实时定量聚合酶链反应和蛋白质印迹检测BIRC2和TRADD的表达水平。使用 Cell Counting Kit-8 和流式细胞术分别检测细胞活力和坏死性凋亡。使用商业试剂盒检测氧化应激标志物，并通过 ELISA 测定测定促炎细胞因子。通过免疫共沉淀实验验证了BIRC2和TRADD之间的相互作用。发现BIRC2和TRADD在LPS介导的C28/I2细胞中高表达。 BIRC2 敲低被证明可以抑制 C28/I2 细胞中 LPS 诱导的细胞活力丧失、坏死性凋亡、氧化应激和炎症。 BIRC2可以与TRADD相互作用并正向调节TRADD的表达。此外，TRADD过表达部分削弱了BIRC2敲低对LPS介导的C28/I2细胞损伤的保护作用。综上所述，BIRC2敲低减轻了LPS介导的C28/I2细胞的坏死性凋亡、氧化应激和炎症，这可能与 TRADD 的调节作用相关，表明治疗 RA 的新靶点。© 2023 作者。约翰·威利出版的《免疫、炎症和疾病》

Rheumatoid arthritis (RA) is a chronic inflammation mediated by an autoimmune response. Baculoviral IAP repeat-containing 2 (BIRC2) and tumor necrosis factor receptor 1-associated death domain protein (TRADD) have been reported to be highly expressed in RA, while their specific roles during RA progression remain unclear. This study aims to explore the specific regulation of BIRC2/TRADD during the progression of RA.C28/I2 cells were stimulated by lipopolysaccharide (LPS) to establish an in vitro RA cellular model. The expression level of BIRC2 and TRADD was examined by quantitative real-time polymerase chain reaction and western blot. Cell Counting Kit-8 and flow cytometry assays were performed to examine cell viability and necroptosis, respectively. The oxidative stress markers were detected using commercial kits, and the pro-inflammatory cytokines were measured by ELISA assay. The interaction between BIRC2 and TRADD was verified by co-immunoprecipitation assay.BIRC2 and TRADD were discovered to be highly expressed in LPS-mediated C28/I2 cells. BIRC2 knockdown was demonstrated to inhibit LPS-induced cell viability loss, necroptosis, oxidative stress, and inflammation in C28/I2 cells. BIRC2 could interact with TRADD and positively regulate TRADD expression. In addition, the protective role of BIRC2 knockdown against LPS-mediated injuries in C28/I2 cells was partly weakened by TRADD overexpression.In summary, BIRC2 knockdown alleviated necroptosis, oxidative stress, and inflammation in LPS-mediated C28/I2 cells, which might correlate to the regulatory role of TRADD, indicating a novel target for the treatment of RA.© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.