International forum of allergy & rhinology · 2022
Eosinophil-derived interferon-γ drives transmembrane protein 119-induced new bone formation in chronic rhinosinusitis with nasal polyps.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Jo Sungsin, Jin Bong Joon, Lee Seung Hoon, Jo Hye-Ryeong, Park Joo Mi, Hwang Kyung-Gyun, Rho Mina, Kim Tae-Hwan, Cho Seok Hyun
Аннотация
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory sinonasal disease characterized by eosinophilic infiltration and new bone formation. These changes indicate the severity and prognosis of CRSwNP and may be closely linked to each other.
METHODS: We performed RNA sequencing to screen specific osteogenic molecules and validated transmembrane protein 119 (TMEM119) expression by quantitative polymerase chain reaction (qPCR) and immunohistochemistry analyses. TMEM119 knockdown was performed to observe the downregulation of bone mineralization. We validated the bone-forming activity of interferon-γ (IFN-γ) and its signaling pathways in cultured primary sinus bone cells. Cellular sources of IFN-γ were identified using immunohistochemistry and immunofluorescence analyses. Interleukin-4-eosinophil-IFN-γ axis and the effect of dupilumab were investigated in Eol-1 cells.
RESULTS: We observed elevated IFN-γ levels and eosinophils in the nasal fluid and predominantly eosinophil-derived IFN-γ in the sinus mucosa of patients with CRSwNP. TMEM119 expression and bone-forming activities were increased in the osteitic and primary sinus bone cells of CRSwNP. IFN-γ treatment enhanced bone mineralization and TMEM119 expression via signal transducer and activator of transcription 1 (STAT1) signaling. Moreover, TMEM119 knockdown inhibited sinus bone cell mineralization and dupilumab attenuated IFN-γ secretion by IL4-stimulated Eol-1 cells.
CONCLUSION: Eosinophil-derived IFN-γ promotes the bone-forming activities of sinus bone cells via the STAT1-TMEM119 signaling pathway. Interleukin-4-eosinophil-IFN-γ axis may be crucial for TMEM119-mediated new bone formation in CRSwNP.
METHODS: We performed RNA sequencing to screen specific osteogenic molecules and validated transmembrane protein 119 (TMEM119) expression by quantitative polymerase chain reaction (qPCR) and immunohistochemistry analyses. TMEM119 knockdown was performed to observe the downregulation of bone mineralization. We validated the bone-forming activity of interferon-γ (IFN-γ) and its signaling pathways in cultured primary sinus bone cells. Cellular sources of IFN-γ were identified using immunohistochemistry and immunofluorescence analyses. Interleukin-4-eosinophil-IFN-γ axis and the effect of dupilumab were investigated in Eol-1 cells.
RESULTS: We observed elevated IFN-γ levels and eosinophils in the nasal fluid and predominantly eosinophil-derived IFN-γ in the sinus mucosa of patients with CRSwNP. TMEM119 expression and bone-forming activities were increased in the osteitic and primary sinus bone cells of CRSwNP. IFN-γ treatment enhanced bone mineralization and TMEM119 expression via signal transducer and activator of transcription 1 (STAT1) signaling. Moreover, TMEM119 knockdown inhibited sinus bone cell mineralization and dupilumab attenuated IFN-γ secretion by IL4-stimulated Eol-1 cells.
CONCLUSION: Eosinophil-derived IFN-γ promotes the bone-forming activities of sinus bone cells via the STAT1-TMEM119 signaling pathway. Interleukin-4-eosinophil-IFN-γ axis may be crucial for TMEM119-mediated new bone formation in CRSwNP.