Mechanism of interferon-gamma production by monocytes stimulated with myeloperoxidase and neutrophil extracellular traps
| Autor: | Shinji Narahara, Arisa Sakamoto, Rui Yamaguchi, Toshitaka Yamamoto, Hiroyuki Sugiuchi, Jin Kawata, Yasuo Yamaguchi, Tomomichi Ono, Eiji Hirose, Yasuji Ishimaru |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Neutrophils
Gene Expression Extracellular Traps Monocytes Interferon-gamma Extracellular medicine Humans Interferon gamma Enzyme Inhibitors Molecular Biology Cells Cultured Peroxidase biology Interferon-gamma production Monocyte Interleukin Cell Biology Hematology Neutrophil extracellular traps Molecular biology medicine.anatomical_structure Myeloperoxidase Neutrophil elastase biology.protein Molecular Medicine Cytokines medicine.drug |
| Zdroj: | Blood cells, moleculesdiseases. 55(2) |
| ISSN: | 1096-0961 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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