TRIM27 enhances NF-κB/MAPK activation by ubiquitinating and degrading TRAF3 to drive asthma-induced airway inflammation.

BACKGROUND

Asthma is a chronic inflammatory airway disease, and airway epithelial cell injury is closely associated with disease progression. TRIM27, as an E3 ubiquitin ligase, plays a significant role in immune-inflammatory responses. This study aims to investigate the role of TRIM27 in airway epithelial cell injury and inflammation.

METHODS

House dust mite extract (HDM)-induced mouse or 16HBE cell models were constructed to simulate asthma in vivo and in vitro. Lung histopathological injury was assessed via HE and PAS staining. Bronchoalveolar lavage fluid (BALF) inflammatory cell counts and ELISA were used to measure inflammation levels. Cell viability and apoptosis was detected by CCK-8, flow cytometry and TUNEL staining. RT-qPCR and Western blot were employed to detect related gene and protein expression.

RESULTS

TRIM27 was upregulated in both in vivo and in vitro asthma models. TRIM27 knockdown alleviated HDM-induced lung histopathological damage in mice, reduced goblet cell hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In vitro experiments showed that TRIM27 knockdown partially restored HDM-induced decline in cell viability, inhibited apoptosis, ROS generation, and inflammatory cytokine release. Mechanistic studies revealed that HDM stimulation activated the NF-κB/MAPK pathway, while TRIM27 knockdown suppressed its activation. Further research demonstrated that TRIM27 activates the NF-κB/MAPK pathway by promoting TRAF3 ubiquitination and degradation. TRAF3 knockdown can weaken the beneficial effects of TRIM27 knockdown.

CONCLUSION

TRIM27 activates the NF-κB/MAPK signaling pathway by promoting TRAF3 ubiquitination and degradation, thereby exacerbating airway epithelial cell injury and inflammatory response, and promoting asthma progression.