Chronic inflammation of nasal mucosal tissue is an obvious feature of allergic rhinitis. Pentraxin 3 (PTX3) is a member of the pentraxin family and plays important roles in inflammation. We aimed to investigate the roles and mechanisms of PTX3 in inflammatory factors and MUC5AC production in human nasal epithelia cells. Loss- and gain-of-function experiments were performed. We found that the silencing of PTX3 dramatically blocked the expression of interleukin (IL)-6, IL-8, IL-1β, and MUC5AC induced by lipopolysaccharide (LPS). Gain-of-function of PTX3 displayed the opposite results. Interestingly, the ablation of PTX3 blocked activation of the PI3K/Akt signaling pathway, whereas the administration of an agonist of PI3K, 740Y-P, partially reversed the inhibitory functions of PTX3 silencing on inflammation and MUC5AC production. Moreover, PTX3 was a positive regulator of TWIST1, which is one of the transcription factors of PTX3. We noticed that TWIST1 downregulation reduced the expression of PTX3. Furthermore, chromatin immunoprecipitation assay and dual-luciferase reporter assay demonstrated that TWIST1 could bind to the promoter of PTX3. Importantly, the depletion of TWIST1 attenuated the LPS-mediated expression and secretion of inflammatory cytokines, whereas these effects were partially abolished upon PTX3 overexpression. Taken together, our findings revealed that the PTX3/TWIST1 feedback loop modulates LPS-induced inflammation and MUC5AC production via the PI3K/Akt signaling pathway.
Keywords: MUC5AC; PI3K/Akt signaling pathway; TWIST1; inflammation; nasal epithelial cells; pentraxin 3 (PTX3).