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.
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.
Björnberg
F
F
Department of Medicine, University of Lund, Sweden.
Lantz
M
M
Gullberg
U
U
D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D018124:Receptors, Tumor Necrosis Factor; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases; D013755:Tetradecanoylphorbol Acetate