USP22 promotes pro-inflammatory responses in Pseudomonas aeruginosa-induced keratitis by targeting TRAF6

Abstract

Background Pseudomonas aeruginosa (PA)-induced keratitis is characterized by inflammatory epithelial edema, stromal infiltration, corneal ulceration, and can lead to vision loss. In the present study, we aim to study the effect of ubiquitin-specific protease 22 (USP22) on PA-induced keratitis. Methods Lentivirus containing control plasmid or shRNA targeting USP22 were used to silence the expression of USP22 in mouse corneas and cultured RAW264.7 cells, the inflammatory processes were detected. Results We found the expression level of USP22 was significantly increased in both mouse corneas and cultured RAW264.7 cells after PA stimulation. In addition, we observed that silencing of USP22 attenuate disease progression, downregulate NF-κB pathway and suppressed the expression of pro-inflammatory cytokines after PA stimulation. Most importantly, we found the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) was decreased by silencing of USP22, and USP22 was found to remove K48-linked poly-ubiquitination chains from TRAF6 to stabilize TRAF6 expression after PA infection. Conclusion This data indicated USP22 as a positive regulator of pro-inflammatory responses in PA induced keratitis.