AutoriMagnone M; Sturla L; Jacchetti E; Scarfi' S; Bruzzone S; Usai C; Guida L; Salis A; Damonte G; De Flora A; Zocchi E
AbstractInhalation of quartz induces silicosis, a lung disease where alveolar macrophages release inflammatory mediators, including prostaglandin-E2 (PGE2) and tumor necrosis factor ? (TNF-?). Here we report the pivotal role of abscisic acid (ABA), a recently discovered human inflammatory hormone, in silica-induced activation of murine RAW264.7 macrophages and of rat alveolar macrophages (AMs). Stimulation of both RAW264.7 cells and AMs with quartz induced a significant increase of ABA release (5- and 10-fold, respectively), compared to untreated cells. In RAW264.7 cells, autocrine ABA released after quartz stimulation sequentially activates the plasma membrane receptor LANCL2 and NADPH oxidase, generating a Ca2+ influx resulting in NF? B nuclear translocation and PGE2 and TNF-? release (3-, 2-, and 3.5-fold increase, respectively, compared to control, unstimulated cells). Quartz-stimulated RAW264.7 cells silenced for LANCL2 or preincubated with a monoclonal antibody against ABA show an almost complete inhibition of NF? B nuclear translocation and PGE2 and TNF-? release compared to controls electroporated with a scramble oligonucleotide or preincubated with an unrelated antibody. AMs showed similar early and late ABA-induced responses as RAW264.7 cells. These findings identify ABA and LANCL2 as key mediators in quartz-induced inflammation, providing possible new targets for antisilicotic therapy.--Magnone, M., Sturla, L., Jacchetti, E., Scarfì, S., Bruzzone, S., Usai, C., Guida, L., Salis, A., Damonte, G., De Flora, A., Zocchi, E. Autocrine abscisic acid plays a key role in quartz-induced macrophage activation.
RivistaThe Faseb Journal
Impact factor
Pagina inizio1271
Pagina fine1261
Autori IBFCesare USAI, Emanuela JACCHETTI
Linee di Ricerca IBFMD.P01.001.001