TIPE2 Protects Bronchial Epithelial Cells From Pyroptosis and Oxidative Stress by Interacting With the E3 Ubiquitin Ligase FBW1A in Asthmatic Mice.

Dysfunction of respiratory epithelial cells is acknowledged as an important pathogenesis of asthma. Tumor necrosis factor-α induced protein 8 like-2 (TNFAIP8L2 or TIPE2) is a famous suppressor of hyperinflammation, which has been involved in regulating asthma progression, however, its role in pyroptosis and oxidative stress of bronchial epithelial cells is still unclear. 1 μg/mL LPS and 50 ng/mL IL-13 was used to induce dysfunction of human bronchial epithelial cells BEAS-2B, and TIPE2 expression was detected at different time points after incubation. Next, TIPE2 expression vector (pcDNA-TIPE2) was transfected into BEAS-2B cells to investigate its involvement in LPS/IL-13-induced pyroptosis and oxidative stress. Then, bioinformatics analysis and co-immunoprecipitation(co-IP) assay were used to verify the binding protein of TIPE2, and rescue experiments were performed to validate the molecular mechanism through which TIPE2 regulated pyroptosis and oxidative stress of BEAS-2B cells. Finally, ovalbumin (OVA) was used to establish an asthmatic animal model in Balb/c female mice, adenovirus-mediated overexpression vector of TIPE2 (Ad-TIPE2) was applied to administrate the asthmatic mice, and the effect of TIPE2 on the progression of asthma was investigated. LPS/IL-13 treatment induced cell death (PI