title: Tripartite Motif 8 (TRIM8) Positively Regulates Pro-inflammatory Responses in Pseudomonas aeruginosa-Induced Keratitis Through Promoting K63-Linked Polyubiquitination of TAK1 Protein.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Chengde Medical University, Chengde, 06700, Hebei, China.
authors.forename: Litao
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Chengde Medical University, Chengde, 06700, Hebei, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Chengde Medical University, Chengde, 06700, Hebei, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Orthopedic Trauma, Affiliated Hospital of Chengde Medical University, Chengde, 06700, Hebei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Chengde Medical University, Chengde, 06700, Hebei, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Chengde Medical University, Chengde, 06700, Hebei, China. tanxiaobo_chengde@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Chengde Medical University, Chengde, 06700, Hebei, China. zhangtiemin1956@126.com.
authors.forename: Tiemin
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D003315:Cornea / Q000378:metabolism / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000382:microbiology; D007634:Keratitis / Q000382:microbiology* / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011550:Pseudomonas aeruginosa; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D044767:Ubiquitin-Protein Ligases; D000099151:MAP Kinase Kinase Kinase 7; C485964:Trim8 protein, mouse
keywords: TAK1; TRIM8; keratitis; polyubiquitination