Autocrine abscisic acid plays a key role in quartz-induced macrophage activation.

Abstract

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-α). 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.

• Authors: Mirko Magnone, Laura Sturla, Emanuela Jacchetti, Sonia Scarfì, Santina Bruzzone, Cesare Usai, Lucrezia Guida, Annalisa Salis, Gianluca Damonte, Antonio De Flora, Elena Zocchi
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 26 Issue 3 Pg. 1261-71 (Mar 2012) ISSN: 1530-6860 [Electronic] United States
• PMID: 22042223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• LANCL2 protein, mouse
• Membrane Proteins
• NF-kappa B
• Phosphate-Binding Proteins
• Receptors, Cell Surface
• Tumor Necrosis Factor-alpha
• Quartz
• Abscisic Acid
• tert-Butylhydroperoxide
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• NADPH Oxidases
• Dinoprostone
• Calcium

Topics

• Abscisic Acid (metabolism, pharmacology, physiology)
• Active Transport, Cell Nucleus (drug effects)
• Animals
• Autocrine Communication (physiology)
• Blotting, Western
• Calcium (metabolism)
• Cell Line
• Cell Nucleus (drug effects, metabolism)
• Cells, Cultured
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Enzyme Activation (drug effects)
• Lipid Peroxidation (drug effects)
• Macrophage Activation (drug effects)
• Macrophages (cytology, drug effects, metabolism)
• Macrophages, Alveolar (cytology, drug effects, metabolism)
• Membrane Proteins (genetics, metabolism)
• Mice
• NADPH Oxidases (metabolism)
• NF-kappa B (metabolism)
• Phosphate-Binding Proteins
• Quartz (pharmacology)
• RNA Interference
• Rats
• Receptors, Cell Surface (genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• tert-Butylhydroperoxide (pharmacology)