title: Interferon-γ enhances phorbol myristate acetate-induced cell attachment and tumor necrosis factor production via the NF-κB pathway in THP-1 human monocytic cells.
abstract: During inflammation, activated macrophages express adhesion molecules and produce cytokines that interact with other hematopoietic and stromal cells. THP-1 non-adherent human monocytic cells differentiate into plastic-adherent macrophages via αVβ3 integrin, by ERK activation in the presence of phorbol myristate acetate (PMA). This has proven to be a valuable model for investigating functional monocyte/macrophage diversity. Interferon-γ (IFN-γ) is a Th1-cytokine that is crucial in macrophage activation. In this study, we investigated the effects of IFN-γ on adhesion and the secretion of tumor necrosis factor (TNF) by PMA-stimulated THP-1 cells. IFN-γ is incapable of inducing cell attachment and TNF production; however, it cumulatively upregulated PMA-induced basal adhesion and TNF production. IFN-γ increased αV integrin, ICAM-1 and VCAM-1 expression and among these PMA-induced cell surface adhesion molecules, the blocking antibody for αV integrin suppressed adhesion and TNF production. Furthermore, IFN-γ enhanced PMA-induced NF-κB phosphorylation and not ERK phosphorylation. Accordingly, the NF-κB pathway inhibitor (BAY 11-7082) inhibited the enhancing effect of IFN-γ on adhesion and TNF production. By contrast, the MEK inhibitor (U0126) almost completely eliminated PMA-induced basal adhesion and TNF production. In conclusion, IFN-γ regulates macrophage activation by mediating the NF-κB signaling pathway.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. y-kuri@dermatol.med.kyushu-u.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
mesh_terms: D000906:Antibodies / Q000276:immunology; D002070:Butadienes / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000906:Antibodies; D002070:Butadienes; D039564:Integrin alphaV; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate