title: Mechanism of interferon-gamma production by monocytes stimulated with myeloperoxidase and neutrophil extracellular traps.
abstract: Neutrophil extracellular traps (NETs) have an important role in antimicrobial innate immunity and release substances that may modulate the immune response. We investigated the effects of soluble factors from NETs and neutrophil granule proteins on human monocyte function by using the Transwell system to prevent cell-cell contact. NET formation was induced by exposing human neutrophils to phorbol myristate acetate (PMA). When monocytes were incubated with PMA alone, expression of interleukin (IL)-4, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha mRNA was upregulated, but IL-10, IL-12, and interferon (IFN)-gamma mRNA were not detected. Incubation of monocytes with NETs enhanced the expression of IL-10 and IFN-gamma mRNA, but not IL-12 mRNA. Myeloperoxidase stimulated IFN-gamma production by monocytes in a dose-dependent manner. Both a nuclear factor-kappaB inhibitor (PDTC) and an intracellular calcium antagonist (TMB-8) prevented upregulation of IFN-gamma production. Neither a combined p38alpha and p38beta inhibitor (SB203580) nor an extracellular signal-regulated kinase inhibitor (PD98059) suppressed IFN-gamma production. Interestingly, a combined p38gamma and p38delta inhibitor (BIRB796) significantly decreased IFN-gamma production. These findings suggest that myeloperoxidase induces IFN-gamma production by monocytes via p38gamma/delta mitogen-activated protein kinase.
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Yamaguchi
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Kawata
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Ishimaru
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Sakamoto
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Tomomichi
authors.initials: T
authors.lastname: Ono
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Narahara
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugiuchi
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Hirose
authors.affiliation: Graduate School of Medical Science, Kumamoto Health Science University, Kumamoto, Japan. Electronic address: yamaguti@kumamoto-hsu.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D065206:Extracellular Traps / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D007371:Interferon-gamma; D009195:Peroxidase
keywords: Interferon-gamma; Mannose receptor; Myeloperoxidase; Neutrophil elastase; p38 Mitogen-activated protein kinase