Department of Ophthalmology, Affiliated Hospital of Chengde Medical University, Chengde, 06700, Hebei, China.
Department of Orthopedic Trauma, Affiliated Hospital of Chengde Medical University, Chengde, 06700, Hebei, China.
Inflammation. 2017 Apr;40(2):454-463. doi: 10.1007/s10753-016-0491-3.
Pseudomonas aeruginosa (PA)-induced keratitis is a rapidly progressive ocular infectious disease that often leads to inflammatory epithelial edema, stromal infiltration, tissue destruction, corneal ulceration, and vision loss. In this study, we investigate the role of tripartite motif 8 (TRIM8) in regulating the inflammatory process of PA-induced keratitis. The expression of TRIM8 was increased in mouse corneas and in vitro-cultured macrophages after PA infection. Knockdown of the expression of TRIM8 significantly inhibited the activation of NF-κB signaling and decreased the production of pro-inflammatory cytokines both in vivo and in vitro after infected with PA. Furthermore, we investigated the potential mechanism and we found after PA infection that TRIM8 could promote K63-linked polyubiquitination of transforming growth factor β-activated kinase 1 (TAK1), leading to the activation of TAK1 and enhanced inflammatory responses. Taken together, we demonstrated that TRIM8 has pro-inflammatory effect on PA-induced keratitis and suggest TRIM8 as a potential therapeutic target for keratitis.
铜绿假单胞菌（PA）诱导的角膜炎是一种迅速进展的眼部感染性疾病，常导致炎症性上皮水肿、基质浸润、组织破坏、角膜溃疡和视力丧失。在本研究中，我们研究了三结构域蛋白 8（TRIM8）在调节 PA 诱导的角膜炎炎症过程中的作用。PA 感染后，TRIM8 的表达在小鼠角膜和体外培养的巨噬细胞中增加。TRIM8 表达的敲低显著抑制了 NF-κB 信号的激活，并减少了体内和体外感染 PA 后促炎细胞因子的产生。此外，我们研究了潜在的机制，我们发现 PA 感染后，TRIM8 可以促进转化生长因子β激活激酶 1（TAK1）的 K63 连接多泛素化，导致 TAK1 的激活和炎症反应的增强。总之，我们证明了 TRIM8 对 PA 诱导的角膜炎具有促炎作用，并提示 TRIM8 可能成为角膜炎的潜在治疗靶点。
