TIPE2 suppresses Pseudomonas aeruginosa keratitis by inhibiting NF-κB signaling and the infiltration of inflammatory cells.

BACKGROUND: The role of tumor necrosis factor α (TNF-α) induced protein 8-like-2 (TIPE2) in Pseudomonas aeruginosa (PA) keratitis was explored.

METHODS: Eight-week-old TIPE2 knockout (TIPE2-/-) C57BL/6 mice and their wild-type littermates (WT) were used. Corneal disease was graded at 1, 2, and 3 days post-infection, and slit lamp, clinical score, histopathology, and immunostaining were performed in the infected corneas. The corneas were harvested, and mRNA levels of TNF-α, interleukin-1βIL-1β, and IL-6 were tested. ELISA determined the protein levels, and NF-κB signaling molecules were tested by Western blot. In vitro human corneal epithelial cells (HCECs) were used to determine the relationship between TIPE2 and TAK1. The HCECs were treated with TIPE2 siRNA and LPS to test the NF-κB signaling molecules by Western blot.

RESULTS: PA infection induced a decreased expression of TIPE2 in mouse corneas 2 days post-infection. Compared to the control group, TIPE2-deficient mice were susceptible to infection with PA and showed increased corneal inflammation. Reduced NF-κB signaling and inflammatory cell infiltration were required in the TIPE2-mediated immune modulation.

CONCLUSION: TIPE2 promoted host resistance to PA infection by suppressing corneal inflammation via regulating TAK1 signaling negatively and inhibiting the infiltration of inflammatory cells.