PMID- 8898953 OWN - NLM STAT- MEDLINE DCOM- 19961210 LR - 20061115 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 26 IP - 10 DP - 1996 Oct TI - Expression and cleavage of tumor necrosis factor-alpha and tumor necrosis factor receptors by human monocytic cell lines upon direct contact with stimulated T cells. PG - 2404-9 AB - Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine in inflammatory processes. A variety of mechanisms that modulate its activity have been described, one being its binding to soluble receptors (sTNFR). In this study, we demonstrate that human monocytic cells such as THP-1 respond to direct contact with a membrane preparation of stimulated HUT-78 cells by producing TNF-alpha and by releasing sTNFR-p75, but not sTNFR-p55, with different kinetics. TNF-alpha concentration peaked after 12 h of contact and then decreased, whereas sTNFR-p75 production increased progressively upon cell/cell contact. The decrease in TNF-alpha concentration is not due to trapping of TNF-alpha by its soluble receptors or other soluble or cell-associated molecules, but rather to a proteolytic activity associated to THP-1 cells. On the other hand, the increase in sTNFR-p75 release does not result from an increase in the cleavage of pre-existing cell-associated sTNFR-p75 but from an increase in TNFR-p75 expression, immediately followed by the cleavage of its extracellular domain. Phenylmethylsulfonylfluoride, a serine protease inhibitor, has a negative effect on both TNF-alpha degradation and sTNFR-p75 release by THP-1 cells. Thus, there may be an enzymatic activity associated to THP-1 cells that plays an important role in the neutralization of TNF-alpha activity both by degrading the molecule and by cleaving its receptors at the cell surface. FAU - Vey, E AU - Vey E AD - Department of Internal Medicine, Hopital Cantonal Universitaire, Geneva, Switzerland FAU - Burger, D AU - Burger D FAU - Dayer, J M AU - Dayer JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.21.- (Serine Endopeptidases) SB - IM MH - Cell Membrane/metabolism MH - Humans MH - Lymphocyte Activation MH - Monocytes/immunology/*metabolism MH - Receptors, Tumor Necrosis Factor/*metabolism MH - Serine Endopeptidases/metabolism MH - Signal Transduction MH - Solubility MH - T-Lymphocytes/*immunology MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/*metabolism EDAT- 1996/10/01 00:00 MHDA- 1996/10/01 00:01 CRDT- 1996/10/01 00:00 PHST- 1996/10/01 00:00 [pubmed] PHST- 1996/10/01 00:01 [medline] PHST- 1996/10/01 00:00 [entrez] AID - 10.1002/eji.1830261021 [doi] PST - ppublish SO - Eur J Immunol. 1996 Oct;26(10):2404-9. doi: 10.1002/eji.1830261021.