title: Molecular mechanisms regulating the synergism between IL-32γ and NOD for the activation of eosinophils.
abstract: 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-32γ 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-32γ was more capable of activating eosinophils than its isotype variant IL-32α and exhibited synergistic effect with NOD1 ligand iE-DAP and NOD2 ligand MDP on the induction of allergic inflammation-related IL-1β, TNF-α, and chemokines CXCL8, CCL3, and CCL4 (P<0.05). Moreover, IL-32γ 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-32γ and NOD ligands was dependent on the activation of intracellular caspase 1, ERKs, p38 MAPK, and NF-κB 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-32γ 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-32γ, can synergize the activation of eosinophils interacting with bronchial epithelial cells.
authors.affiliation: 2.The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, China. ck-wong@cuhk.edu.hk.
authors.forename: Chun-Kwok
authors.initials: CK
authors.lastname: Wong
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.forename: Christopher Wai-Kei
authors.initials: CW
authors.lastname: Lam
mesh_terms: D018821:CD18 Antigens / Q000502:physiology; D018925:Chemokines / Q000096:biosynthesis; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D053474:Nod1 Signaling Adaptor Protein / Q000502:physiology*; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology*
chemical_list: D018821:CD18 Antigens; D018925:Chemokines; D016207:Cytokines; C496971:IL32 protein, human; D007378:Interleukins; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D018799:Intercellular Adhesion Molecule-1
keywords: bronchial epithelial cells; extracellular DNA traps; signal transduction