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Cytokines involved in monocyte mediated tumor cell death and growth inhibition in serum‐free medium
Author(s) -
Van Der Bosch Jürgen,
Rüller Elisabeth,
Ernst Martin,
Schade Ulrich F.,
Mathison John C.,
Rüller Stephan,
Schlaak Max
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041520321
Subject(s) - cytokine , programmed cell death , proinflammatory cytokine , lytic cycle , tumor necrosis factor alpha , context (archaeology) , monocyte , cell growth , growth inhibition , cell culture , signal transduction , chemistry , immunology , biology , microbiology and biotechnology , biochemistry , apoptosis , inflammation , genetics , paleontology , virus
Abstract In a serum‐free culture system, the release of TNF, II‐1, II‐6, IFN‐α, and IFN‐β during interaction of elutriated human monocytes (MO) with human tumor cells (TC) was studied by ELISA‐technique. Contributions of these cytokines to inhibition of TC‐growth and to induction of TC‐death by supernatants (SU) gained from such MO/TC‐interaction cultures were investigated using affinity chromatography for removal of individual cytokines. Although the TC used are relatively insensitive to recombinant human TNF, withdrawal of TNF causes 50% to 75% reduction of SU‐induced TC‐death rates, suggesting that susceptibility to TNF is raised during MO/TC‐interaction by the other cytokines. Individual removal of other cytokines does not cause reduction of SU‐mediated TC‐death. However, combined withdrawal of II‐1 and IFN‐α/β causes in 2 of 4 TC‐lines significant reduction of TC‐death. Combined removal of TNF, IFN‐α/β, II‐1, and II‐6 leads to complete prevention of SU‐mediated growth inhibitory and lytic effects, suggesting that besides these cytokines other signals are not involved significantly. SU‐effects can be mimicked by appropriate combinations of authentic cytokines. The response of TC to SU‐or cytokine‐exposure is strikingly dependent on TC‐density, leading at subconfluent TC‐density exclusively to inhibition of growth and at postconfluent TC‐density to induction of cell death. The principal effect of SU or cytokine combinations in this context seems to be the activation of growth inhibitory signal transduction pathways leading to TC‐death in postconfluent TC‐populations exclusively if growth stimulatory pathways are activated at the same time. Mouse L cells do not follow this reaction pattern: Their death is exclusively dependent on the presence of TNF in SU and they die upon SU‐exposure at postconfluent as well as at subconfluent cell density. © 1992 Wiley‐Liss, Inc.