Molecular mechanisms regulating the synergism between IL-32 gamma and NOD for the activation of eosinophils
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AbstractBacterial NOD1,2, together with IL-32, can synergize the activation of eosinophils interacting with bronchial epithelial cells, via novel intracellular mechanisms. IL-32 is a proinflammatory cytokine associated with infections, autoimmune diseases, and allergic asthma. In the present study, we elucidated the synergistic effect of IL-32 and NOD ligand on the activation of human eosinophils, principal effector cells for allergic inflammation, and the underlying mechanisms. Specific IL-32-binding protein, PR3, was found to localize on the cell surface and in the cytoplasm of eosinophils. IL-32 was more capable of activating eosinophils than its isotype variant IL-32 and exhibited synergistic effect with NOD1 ligand iE-DAP and NOD2 ligand MDP on the induction of allergic inflammation-related IL-1, TNF-, and chemokines CXCL8, CCL3, and CCL4 (P<0.05). Moreover, IL-32 and iE-DAP or MDP induced the significant up-regulation of the cell-surface expression of adhesion molecule CD18 and ICAM-1 on eosinophils. Synergism between IL-32 and NOD ligands was dependent on the activation of intracellular caspase 1, ERKs, p38 MAPK, and NF-B pathways in eosinophils. The further-enhanced CD18 and ICAM-1 expression and production of cytokines and chemokines were observed in eosinophils cocultured with human bronchial epithelial BEAS-2B cells. Furthermore, combined treatment of IL-32 and NOD ligand could activate the release of eosinophil extracellular DNA traps, thereby implying the pathogen-defense mechanisms of eosinophils. Together, the above study provides pivotal immunological mechanisms by which bacterial infection-mediated activation of NOD1,2, together with IL-32, can synergize the activation of eosinophils interacting with bronchial epithelial cells.
All Author(s) ListWong CK, Dong J, Lam CWK
Journal nameJournal of Leukocyte Biology
Detailed descriptiondoi: 10.1189/jlb.0813452.
Volume Number95
Issue Number4
PublisherSociety for Leukocyte Biology
Pages631 - 642
LanguagesEnglish-United Kingdom
Keywordsbronchial epithelial cells; extracellular DNA traps; signal transduction
Web of Science Subject CategoriesCell Biology; CELL BIOLOGY; Hematology; HEMATOLOGY; Immunology; IMMUNOLOGY

Last updated on 2020-17-10 at 00:02