Relaxed specificity of matrix metalloproteinases (MMPS) and TIMP insensitivity of tumor necrosis factor-α (TNF-α) production suggest the major TNF-α converting enzyme is not an MMP

Roy A. Black, Fiona H. Durie, Carol Otten-Evans, Robert Miller, Jennifer L. Slack, David H. Lynch, Beverly Castner, Kendall M. Mohler, Mary Gerhart, Richard S. Johnson, Yoshifumi Itoh, Yasunori Okada, Hideaki Nagase

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Abstract

Tumor necrosis factor-α is released from cells by a proteolytic cleavage. Previous work suggested that a specific, non-matrix metalloproteinase carries out this cleavage, but matrix metalloproteinases have also been implicated. In this paper, we report that none of the matrix metalloproteinases tested cleaved peptide substrates as specifically as the non-matrix metalloproteinase. A matrix metalloproteinase did process tumor necrosis factor-α extracted from COS cells, but neither tissue inhibitor of metalloproteinases-1 nor -2 blocked tumor necrosis factor-α processing by human monocytes. Moreover, tissue inhibitor of metalloproteinases-1 had at most a partial effect on the in vivo release of the cytokine in mice. We conclude. that a non-matrix metalloproteinase is the major physiological tumor necrosis factor-α convertase.

Original languageEnglish
Pages (from-to)400-405
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume225
Issue number2
DOIs
Publication statusPublished - 1996 Aug 14

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ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Black, R. A., Durie, F. H., Otten-Evans, C., Miller, R., Slack, J. L., Lynch, D. H., Castner, B., Mohler, K. M., Gerhart, M., Johnson, R. S., Itoh, Y., Okada, Y., & Nagase, H. (1996). Relaxed specificity of matrix metalloproteinases (MMPS) and TIMP insensitivity of tumor necrosis factor-α (TNF-α) production suggest the major TNF-α converting enzyme is not an MMP. Biochemical and Biophysical Research Communications, 225(2), 400-405. https://doi.org/10.1006/bbrc.1996.1186