Molecular and Therapeutic Significance of sNASP-TRAF6 axis in DEP-exacerbated airway allergic asthma

Diesel exhaust particles (DEP) has considered as a major emission source of air pollutants from the incomplete combustion of fossil fuel in motor vehicle or heavy-duty industries, which can exacerbate allergic inflammation in the lung. Here, we demonstrated that sNASP-TRAF6 axis is a regulatory checkpoint of TGF-β1 signaling to modulate the DEP-induced allergic response. In our studies, we showed that both DEP and TGF-β1 challenge decreased expression of sNASP via SUMO-dependent proteasomal degradation, which leads to active TRAF6 pathway, and concomitantly caused E-cadherin loss and increase proallergic cytokines (TSLP, IL-25 and IL-33) in bronchial epithelial cells. Similarly, silencing of TRAF6 can restore the E-cadherin loss and decrease proallergic cytokines production. Our data also indicated that administration of cell permeable PEP-sNASP peptide can be therapeutic approach to prevent DEP-induced barrier disruption via targeting TRAF6 signaling. Thus, we suggested that sNASP-TRAF6 axis regulate through different downstream mechanisms and that axis itself may be a viable therapeutic target and a biomarker for allergic asthma. <fig><object-id>erj;64/suppl_68/PA5305/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <fig><object-id>erj;64/suppl_68/PA5305/F2</object-id><object-id>F2</object-id><object-id>F2</object-id><graphic></graphic></fig>