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Metalloproteases and serineproteases are involved in the cleavage of the two tumour necrosis factor (TNF) receptors to soluble forms in the myeloid cell lines U-937 and THP-1

Björnberg, F LU ; Lantz, M LU and Gullberg, U LU (1995) In Scandinavian Journal of Immunology 42(4). p.24-418
Abstract

The proteolytic processing of the two TNF receptors (TNF-R55 and TNF-R75) into soluble forms was investigated in the myeloid cell lines U-937 and THP-1. Phorbol myristate acetate (PMA) rapidly stimulated release of soluble forms of both TNF-receptors. Incubations were made with PMA and protease inhibitors directed against different target protease groups. The serineprotease inhibitors TPCK and dichloroisocoumarin and the metalloprotease inhibitor 1,10-phenanthroline reduced PMA-induced release of both soluble receptor forms with about 60-70%. Furthermore, 1,10-phenanthroline also reduced PMA-induced down-regulation of TNF-receptors in both cell lines as judged by TNF-binding to cells. Reduced down-regulation and TNF-receptor shedding by... (More)

The proteolytic processing of the two TNF receptors (TNF-R55 and TNF-R75) into soluble forms was investigated in the myeloid cell lines U-937 and THP-1. Phorbol myristate acetate (PMA) rapidly stimulated release of soluble forms of both TNF-receptors. Incubations were made with PMA and protease inhibitors directed against different target protease groups. The serineprotease inhibitors TPCK and dichloroisocoumarin and the metalloprotease inhibitor 1,10-phenanthroline reduced PMA-induced release of both soluble receptor forms with about 60-70%. Furthermore, 1,10-phenanthroline also reduced PMA-induced down-regulation of TNF-receptors in both cell lines as judged by TNF-binding to cells. Reduced down-regulation and TNF-receptor shedding by 1,10-phenanthroline was reversed by Zn2+, indicating involvement of a Zn(2+)-dependent metalloprotease. Thus, both serine proteases and metalloproteases are involved in the processing of TNF-receptors.

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author
organization
publishing date
type
Contribution to journal
publication status
published
keywords
Enzyme Inhibitors, Humans, Metalloendopeptidases, Receptors, Tumor Necrosis Factor, Serine Endopeptidases, Signal Transduction, Tetradecanoylphorbol Acetate, Tumor Cells, Cultured
in
Scandinavian Journal of Immunology
volume
42
issue
4
pages
7 pages
publisher
Wiley-Blackwell
external identifiers
  • Scopus:0028971793
ISSN
0300-9475
language
English
LU publication?
yes
id
5f154dad-bab6-4068-a796-c36a2a912a0d
date added to LUP
2016-06-01 10:08:25
date last changed
2016-06-02 04:00:00
@misc{5f154dad-bab6-4068-a796-c36a2a912a0d,
  abstract     = {<p>The proteolytic processing of the two TNF receptors (TNF-R55 and TNF-R75) into soluble forms was investigated in the myeloid cell lines U-937 and THP-1. Phorbol myristate acetate (PMA) rapidly stimulated release of soluble forms of both TNF-receptors. Incubations were made with PMA and protease inhibitors directed against different target protease groups. The serineprotease inhibitors TPCK and dichloroisocoumarin and the metalloprotease inhibitor 1,10-phenanthroline reduced PMA-induced release of both soluble receptor forms with about 60-70%. Furthermore, 1,10-phenanthroline also reduced PMA-induced down-regulation of TNF-receptors in both cell lines as judged by TNF-binding to cells. Reduced down-regulation and TNF-receptor shedding by 1,10-phenanthroline was reversed by Zn2+, indicating involvement of a Zn(2+)-dependent metalloprotease. Thus, both serine proteases and metalloproteases are involved in the processing of TNF-receptors.</p>},
  author       = {Björnberg, F and Lantz, M and Gullberg, U},
  issn         = {0300-9475},
  keyword      = {Enzyme Inhibitors,Humans,Metalloendopeptidases,Receptors, Tumor Necrosis Factor,Serine Endopeptidases,Signal Transduction,Tetradecanoylphorbol Acetate,Tumor Cells, Cultured},
  language     = {eng},
  number       = {4},
  pages        = {24--418},
  publisher    = {ARRAY(0x8db3b70)},
  series       = {Scandinavian Journal of Immunology},
  title        = {Metalloproteases and serineproteases are involved in the cleavage of the two tumour necrosis factor (TNF) receptors to soluble forms in the myeloid cell lines U-937 and THP-1},
  volume       = {42},
  year         = {1995},
}