Outside-to-inside signal through the membrane, TNF-α induces E-selectin (CD62E) expression on activated human CD4+ T cells

S. I. Harashima, T. Horiuchi, N. Hatta, C. Morita, M. Higuchi, T. Sawabe, H. Tsukamoto, T. Tahira, K. Hayashi, S. Fujita, Y. Niho

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112 Citations (Scopus)


The membrane TNF-α is known to serve as a precursor of the soluble form of TNF-α. Although it has been reported the biological functions of the membrane TNF-α as a ligand, the outside-to-inside (reverse) signal transmitted through membrane TNF-α is poorly understood. Here we report a novel function mediated by outside-to-inside signal via membrane TNF-α into the cells expressing membrane TNF-α. Activation by anti-TNF-α Ab against membrane TNF-α on human T cell leukemia virus (HTLV) I-infected T cell line, MT-2, or PHA-activated normal human CD4+ T cells resulted in the induction of an adhesion molecule, E-selectin (CD62E), on the cells with the peak of 12-24 h, which completely disappeared by 48 h. When wild-type or mutant membrane TNF-α (R78T/S79T) resistant to proteolytic cleavage was introduced into Jurkat or HeLa cells, E-selectin was induced by the treatment with anti-TNF-α Ab with the similar kinetics. Membrane TNF-α-expressing Jurkat cells also up-regulated E-selectin when brought into cell-to-cell contact with TNF receptor-expressing HeLa cells. Northern blot analysis and RT-PCR analysis showed that the membrane TNF-α-mediated E-selectin expression was up-regulated at the level of transcription. These results not only confirmed our previous findings of reverse signaling through membrane TNF-α, but also presented evidence that E-selectin was inducible in cell types different from endothelial cells. It is strongly suggested that membrane TNF-α is a novel proinflammatory cell surface molecule that transmits bipolar signals in local inflammation.

Original languageEnglish
Pages (from-to)130-136
Number of pages7
JournalJournal of Immunology
Issue number1
Publication statusPublished - Jan 1 2001

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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