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

Abstract

Pseudomonas aeruginosa (PA)‑induced keratitis is characterized by inflammatory epithelial edema, stromal infiltration, corneal ulceration and can lead to vision loss. The present study aimed to study the effect of ubiquitin‑specific protease 22 (USP22) on PA‑induced keratitis. Using RT‑qPCR and western blotting, significantly increased expression of USP22 was identified in mouse corneas and cultured RAW264.7 cells following PA stimulation. In addition, the results of in vivo experiments, western blot assay and ELISA suggested that the silencing of USP22 attenuated disease progression, downregulated the NF‑κB pathway and suppressed the expression of pro‑inflammatory cytokines following PA stimulation. Notably, it was identified that the expression of tumor necrosis factor receptor‑associated factor 6 (TRAF6) was decreased by silencing of USP22 and USP22 was found to remove lysine 48‑linked poly‑ubiquitination chains from TRAF6 to stabilize TRAF6 expression and these effects were clearly aggravated following PA infection.

Keywords: Pseudomonas aeruginosa; keratitis; tumor necrosis factor receptor‑associated factor 6; ubiquitin‑specific protease 22.