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	Litao Guo, Weili Dong, Xiaoxiao Fu, Jing Lin, Zhijun Dong, Xiaobo Tan, Tiemin Zhang
Journal	Inflammation (Inflammation) Vol. 40 Issue 2 Pg. 454-463 (Apr 2017) ISSN: 1573-2576 [Electronic] United States
PMID	27995356 (Publication Type: Journal Article)
Chemical References	Carrier Proteins Cytokines NF-kappa B Nerve Tissue Proteins Trim8 protein, mouse Ubiquitin-Protein Ligases MAP Kinase Kinase Kinases MAP kinase kinase kinase 7
Topics	Animals Carrier Proteins (physiology) Cornea (metabolism, microbiology) Cytokines (metabolism) Inflammation (microbiology) Keratitis (microbiology, pathology) MAP Kinase Kinase Kinases (metabolism) Macrophages (metabolism, pathology) Mice NF-kappa B (metabolism) Nerve Tissue Proteins (physiology) Pseudomonas aeruginosa Ubiquitin-Protein Ligases Ubiquitination

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