Interleukin‐17A potentiates interleukin‐13‒induced eotaxin‐3 production by human nasal epithelial cells from patients with allergic rhinitis

Abstract

Background: Interleukin (IL)-17A is involved in the pathogenesis of allergic rhinitis (AR). Increased expression of IL-17A is correlated with disease severity and nasal eosinophilia. However, the molecular mechanisms by which IL-17A contributes to T-helper 2 cytokine IL-13-driven pathology in AR remain unclear. We sought to obtain mechanistic insight into how IL-17A and IL-13 regulate the epithelial production of eotaxin-3 representing eosinophilic inflammation in AR. Methods:Human nasal epithelial cells (HNECs) from AR patients were cultured and stimulated with IL-17A, IL-13, or IL-17A and IL-13. Phosphorylated signal transducer activator of transcription 6 (p-STAT6) and suppressor of cytokine signaling 1 (SOCS1) in HNECs were assayed using Western blo ing. Immunocytochemistry was used to determine p-STAT6-positive expression in the cells. Eotaxin-3 expression in the cells and culture supernatants was evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assays. Results:Stimulation with IL-13 alone induced STAT6 phosphorylation and promoted p-STAT6 nuclear translocation, leading to eotaxin-3 production by HNECs. These effects were further enhanced by cotreatment with IL-13 and IL-17A, whereas IL-17A alone had no impact on STAT6 or eotaxin-3 expression. Incubation with IL-17A or IL-13 increased the level of SOCS1 protein in the cells, whereas the addition of IL-17A a enuated IL-13-induced SOCS1 expression.Conclusion: IL-17A potentiated IL-13-driven STAT6 activation through the downregulation of SOCS1 expression, leading to enhancement of eotaxin-3 production by HNECs. These factors contributed to eosinophilic inflammation in AR. C 2019 ARS-AAOA, LLC. Key Words:allergic rhinitis; interleukin-17A; interleukin-13; eotaxin-3; signal transducer activator of transcription 6; suppressor of cytokine signaling 1 How to Cite this Article: Wang WW, Zhu K, Yu HW, Pan YL. Interleukin-17A potentiates interleukin-13-induced eotaxin-3 production by human nasal epithelial cells from patients with allergic rhinitis. Int Forum Allergy Rhinol. 2019;9:1327-1333.A llergic rhinitis (AR) is a chronic inflammatory disease with a prevalence of 10%-40%. 1 CD4 + T-helper (Th) cells play a vital role in local mucosal immune responses of allergic airway diseases. 2 AR has long been hypothesized as the result of dysregulation of the balance between Th1 and

LncRNA FGD5-AS1 Alleviates Inflammation in Allergic Rhinitis through the miR-223-3p/COX11 Axis

“…2a). Given that IL-13 can induce an inflammatory response in HNEPCs and is commonly used for in vitro studies of AR [19], we employed IL-13 treatment as an experimental model. After utilizing IL-13, we found that FGD5-AS1 expression in HNEPCs was obviously lower than the control group ( p < 0.01), indicating that FGD5-AS1 expression was downregulated in AR cells.…”

Th22 ir Th17 vaidmuo alerginių kvėpavimo takų ligų metu

“…In a Th2 dominant environment, IL-17 can promote eosinophils survival and degranulation, leading to chronic nasal inflammation Moksliniai darbai ir apžvalgos in allergic rhinitis (41). Besides, IL-17 enhances IL-13 induced STAT6 phosphorylation leading to eotaxin -3 production (42). These factors contribute to eosinophilic inflammation.…”

Downregulation of deubiquitinating enzyme USP25 promotes the development of allergic rhinitis by enhancing TSLP signaling in the nasal epithelium

“…Increasing evidence indicates that nasal epithelial cell dysfunction may be the major cause of nasal allergic inflammation (9,10). The nasal epithelium is the first barrier against allergen infiltration and epithelial cell-derived cytokine milieu activates different types of immune cell, thereby acting as a master immune regulator in allergic inflammation (11)(12)(13). Thymic stromal lymphopoietin (TSLP) is one of the primary epithelial-derived cytokines in T helper type 2 (Th2) reactions (14).…”