TSLP Induces Epithelial–Mesenchymal Transition in Nasal Epithelial Cells From Allergic Rhinitis Patients Through TGF-β1/Smad2/3 Signaling

Abstract

Background Airway remodeling is demonstrated in Asian patients with allergic rhinitis (AR). The epithelial–mesenchymal transition (EMT) is one of the key mechanisms underlying airway remodeling. Thymic stromal lymphopoietin (TSLP) is an important contributor to airway remodeling. Although increased TSLP is found in AR, little is known about whether TSLP is involved in airway remodeling through induction of the EMT. Objective We investigated the effect of TSLP on the EMT in human nasal epithelial cells (HNECs) from AR patients. Methods Human nasal epithelial cells from AR patients were stimulated with TSLP in the absence or presence of the preincubation with a selective inhibitor of transforming growth factor beta 1 (TGF-β1) receptor (SB431542). The expression of TGF-β1 in the cells was evaluated by using real-time polymerase chain reaction, Western blotting, and immunocytochemistry. Western blotting and immunocytochemistry were used to assay EMT markers including vimentin, fibroblast-specific protein 1 (FSP1) and E-cadherin, small mothers against decapentaplegic homolog2/3 (Smad2/3), and phosphorylated Smad2/3 in the cells. The levels of extracellular matrix components such as collagens I and III in supernatants were measured by enzyme-linked immunoassay. Morphological changes of the cells were observed under inverted phase-contrast microscope. Results A concentration-dependent increase of TGF-β1 mRNA and protein was observed following stimulation with TSLP. Furthermore, TSLP decreased the expression of E-cadherin protein, but upregulated the production of FSP1 and vimentin proteins along with increased levels of collagens I and III, and the morphology of the cells was transformed into fibroblast-like shape. Additionally, a significant increase was found in phosphorylation of Smad2/3 protein. However, these effects were reversed by SB431542 preincubation. Conclusion TSLP–induced HNECs to undergo the EMT process via TGF-β1-mediated Smad2/3 activation. TSLP is an activator of the EMT in HNECs and might be a potential target for inhibiting EMT and reducing airway remodeling in AR.

Upper Airway Alarmin Cytokine Expression in Asthma of Different Severities

“…Furthermore, no significant changes were observed in IL-33 levels across all GINA categories, which agrees with a recent study on TSLP and IL-33 serum levels in mild asthma patients, showing a slight reduction in sera in mild asthma compared to that in healthy controls [35]. Increased TSLP expression in nasal epithelial cells among those with nasal comorbidities, although not significant, is also consistent with previous studies in allergic rhinitis and chronic rhinosinusitis [36,37].…”

“You are Always a Student, Never a Master: You Have to Keep Moving Forward” Conrad Hall

“…In their study, glucocorticoid-induced transcript I SNP was associated with an increased risk of developing AR when the SNP was present and did show increased symptomatic relief and response to intranasal corticosteroids. Yu et al 7 help further our understanding of the role of thymic stromal lymphopoietin (TSLP) as an activator of the epithelial-mesenchymal transition (EMT) in AR and identify a potential target for inhibiting EMT and reducing airway remodeling. Wang et al 8 utilized an ovalbumin-rat AR model to elucidate the effects of the neurokinin-I receptor (NK-IR) on cytokine normal T-cell expressed and secreted (RANTES).…”