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Autocrine abscisic acid plays a key role in quartz‐induced macrophage activation
Author(s) -
Mag Mirko,
Sturla Laura,
Jacchetti Emanuela,
Scarfì Sonia,
Bruzzone Santina,
Usai Cesare,
Guida Lucrezia,
Salis Annalisa,
Damonte Gianluca,
De Flora Antonio,
Zocchi Elena
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-187351
Subject(s) - abscisic acid , autocrine signalling , key (lock) , macrophage , chemistry , microbiology and biotechnology , biochemistry , biology , ecology , receptor , gene , in vitro
Inhalation of quartz induces silicosis, a lung disease where alveolar macrophages release inflammatory mediators, including prostaglandin‐E 2 (PGE 2 ) and tumor necrosis factor α (TNF‐a). 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 Ca 2+ influx resulting in NFκ B nuclear translocation and PGE 2 and TNF‐α 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 NFκ B nuclear translocation and PGE 2 and TNF‐α 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. FASEB J. 26, 1261‐1271 (2012). www.fasebj.org