Interleukin-17A up-regulates thymic stromal lymphopoietin production by nasal fibroblasts from patients with allergic rhinitis
| Autor: | Wei Wei Wang, Hong Wei Yu, Sheng Wen Shao, Yong Liang Pan, Bo Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
STAT3 Transcription Factor
Thymic stromal lymphopoietin Blotting Western Enzyme-Linked Immunosorbent Assay Thymic stromal lymphopoietin production 03 medical and health sciences 0302 clinical medicine Thymic Stromal Lymphopoietin Medicine Humans 030223 otorhinolaryngology STAT3 biology business.industry Tumor Necrosis Factor-alpha Interleukin-17 NF-kappa B Interleukin General Medicine Fibroblasts JAK2 Inhibitor AZD1480 Rhinitis Allergic Nasal Mucosa Otorhinolaryngology 030220 oncology & carcinogenesis STAT protein Cancer research biology.protein Cytokines Interleukin 17 Janus kinase business |
| Zdroj: | European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 278(1) |
| ISSN: | 1434-4726 |
| Popis: | Emerging evidence has shown that interleukin (IL)-17A is implicated in the pathogenesis of allergic rhinitis (AR). Thymic stromal lymphopoietin (TSLP) orchestrates the immune response toward a Th2 phenotype. Although increased TSLP is found in AR, the contribution of IL-17A in TSLP production by nasal fibroblasts is not well understood. We aimed to investigate the effect and mechanism of IL-17A on TSLP production by human nasal fibroblasts (HNFs) from AR patients. HNFs from AR patients were cultured and stimulated with IL-17A in the absence or presence of a Janus kinase (JAK) 2 or JAK1/3 inhibitor. Western blotting was used to assay phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and nuclear factor-kappa B (NF-κB) p65 in HNFs. The TSLP expression in the cells and culture supernatants was evaluated by real-time polymerase chain reaction and enzyme-linked immunoassay. Stimulation with IL-17A induced STAT3 phosphorylation, which was inhibited by the pretreatment with JAK2 inhibitor AZD1480 or JAK1/3 inhibitor tofacitinib. IL-17A promoted the nuclear translocation of NF-κBp65 protein, leading to increased TSLP production, while the pre-incubation with AZD1480 prior to IL-17A attenuated these effects. However, the pre-incubation with tofacitinib before IL-17A stimulation had no impact on the expression of NF-κBp65 and TSLP. IL-17A up-regulated TSLP production by HNFs through JAK2/NF-κB pathway. Although IL-17A induced STAT3 activation through JAK1/2/3, IL-17A-mediated TSLP expression was not dependent on STAT3 signaling. These observations would provide mechanistic insight into therapeutic strategies to improve the immune and inflammation associated with Th17A in the management of AR. |
| Databáze: | OpenAIRE |
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