Involvement of TWEAK in interferon γ-stimulated monocyte cytotoxicity

Masafumi Nakayama, Nobuhiko Kayagaki, Noriko Yamaguchi, Ko Okumura, Hideo Yagita

Research output: Contribution to journalArticlepeer-review

144 Citations (Scopus)


TWEAK, a new member of the tumor necrosis factor (TNF) family, induces cell death in some tumor cell lines, but its physiological functions are largely unknown. In this study, we investigated the expression and function of TWEAK in human peripheral blood mononuclear cells (PBMCs) by using newly generated anti-human TWEAK mAbs. Although freshly isolated PBMCs expressed no detectable level of TWEAK on their surfaces, a remarkable TWEAK expression was rapidly observed on monocytes upon stimulation with interferon (IFN)-γ but not with IFN-α or lipopolysaccharide. Cytotoxic activity of IFN-γ-stimulated monocytes against human squamous carcinoma cell line HSC3 was inhibited partially by anti-TWEAK mAb alone and almost completely by combination with anti-TRAIL (TNF-related apoptosis-inducing ligand) mAb. These results revealed a novel pathway of monocyte cytotoxicity against tumor cells that is mediated by TWEAK and potentiated by IFN-γ.

Original languageEnglish
Pages (from-to)1373-1379
Number of pages7
JournalJournal of Experimental Medicine
Issue number9
Publication statusPublished - 2000 Nov 6
Externally publishedYes


  • Cytotoxicity
  • IFN-γ
  • Monocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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