Particle and fibre toxicology · 2013
Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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.
Hillegass Jedd M, Miller Jill M, MacPherson Maximilian B, Westbom Catherine M, Sayan Mutlay, Thompson Joyce K, Macura Sherrill L, Perkins Timothy N, Beuschel Stacie L, Alexeeva Vlada, Pass Harvey I, Steele Chad, Mossman Brooke T, Shukla Arti
Аннотация
BACKGROUND: Pleural fibrosis and malignant mesotheliomas (MM) occur after exposures to pathogenic fibers, yet the mechanisms initiating these diseases are unclear.
RESULTS: We document priming and activation of the NLRP3 inflammasome in human mesothelial cells by asbestos and erionite that is causally related to release of IL-1β, IL-6, IL-8, and Vascular Endothelial Growth Factor (VEGF). Transcription and release of these proteins are inhibited in vitro using Anakinra, an IL-1 receptor antagonist that reduces these cytokines in a human peritoneal MM mouse xenograft model.
CONCLUSIONS: These novel data show that asbestos-induced priming and activation of the NLRP3 inflammasome triggers an autocrine feedback loop modulated via the IL-1 receptor in mesothelial cell type targeted in pleural infection, fibrosis, and carcinogenesis.
RESULTS: We document priming and activation of the NLRP3 inflammasome in human mesothelial cells by asbestos and erionite that is causally related to release of IL-1β, IL-6, IL-8, and Vascular Endothelial Growth Factor (VEGF). Transcription and release of these proteins are inhibited in vitro using Anakinra, an IL-1 receptor antagonist that reduces these cytokines in a human peritoneal MM mouse xenograft model.
CONCLUSIONS: These novel data show that asbestos-induced priming and activation of the NLRP3 inflammasome triggers an autocrine feedback loop modulated via the IL-1 receptor in mesothelial cell type targeted in pleural infection, fibrosis, and carcinogenesis.
Предметные рубрики MeSH
AnimalsAsbestos, CrocidoliteAutocrine CommunicationCarrier ProteinsCell Line, TumorCytokinesDose-Response Relationship, DrugEpitheliumHumansInflammasomesInflammation MediatorsInterleukin 1 Receptor Antagonist ProteinMesotheliomaMiceMice, SCIDNLR Family, Pyrin Domain-Containing 3 ProteinPrimary Cell CultureRNA, MessengerReceptors, Interleukin-1Time FactorsTranscription, GeneticXenograft Model Antitumor AssaysZeolites