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

Yuichi Kurihara, Masutaka Furue

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 α vβ3 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.

Original languageEnglish
Pages (from-to)1739-1744
Number of pages6
JournalMolecular medicine reports
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 1 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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