Asthma, a chronic inflammatory airway disease, presents a significant global health burden. This study aimed to elucidate the mechanism by which curcumin modulates tracheal epithelial cell autophagy in asthma, with a specific focus on its interplay with SCGB3A2 and the NF-κB pathway.

An in vitro asthma model was mimicked using 16HBE cells treated with TDI. Concurrently, a TDI-induced asthma model was built in Balb/c mice for in vivo investigations. Cells or mice were subjected to curcumin treatment, and SCGB3A2 was knockdown or overexpressed, to explore the function of SCGB3A2. TNF-α and TPCA-1 were also utilized to mediate activation of NF-κB in vitro. Western blot, qPCR, ELISA, immunofluorescence, and transmission electron microscopy were employed to assess SCGB3A2 expression, NF-κB pathway activation, autophagy, key inflammatory cytokines, and airway remodeling indicators.

TDI stimulation reduced SCGB3A2 expression in 16HBE cells. SCGB3A2 overexpression mitigated TDI-induced inflammation and airway remodeling by inhibiting the NF-κB pathway and enhancing autophagy. Subsequent NF-κB activation partially abrogated these SCGB3A2-mediated protective effects on inflammation, airway remodeling, and autophagy. Curcumin treatment upregulated SCGB3A2, inhibited NF-κB activation, and promoted autophagy; these protective effects were substantially diminished upon SCGB3A2 knockdown. In vivo, curcumin administration ameliorated asthma features, evidenced by reduced airway inflammation, suppressed NF-κB, and enhanced autophagy in tracheal epithelial tissues.

This study reveals that curcumin protects against asthma by modulating the SCGB3A2-NF-κB-autophagy axis. These findings highlight this axis as a novel therapeutic target for asthma.