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Differential regulation of interleukin-12 (IL-12), tumor necrosis factor
alpha, and IL-1 beta production in human myeloid leukemia cell lines and
peripheral blood mononuclear cells
M Kubin, JM Chow and G Trinchieri
Wistar Institute, Philadelphia, PA 19104.
Natural killer cell-stimulatory factor or interleukin-12 (NKSF/IL-12) was
originally identified and purified from the conditioned medium of
Epstein-Barr virus (EBV)-transformed B-cell lines. Phorbol diesters were
observed to be potent stimulators of NKSF/IL-12 production from the B-cell
lines. Although monocytes were found to be the major producers of
NKSF/IL-12 in peripheral blood (PB) in response to lipopolysaccharide (LPS)
or to Staphylococcus aureus, several myeloid leukemia cell lines tested did
not produce detectable NKSF/IL-12 either constitutively or upon stimulation
with phorbol diesters. However, three lines, ML-3, HL-60, and THP-1,
responded to LPS with significant levels of NKSF/IL-12 production, whereas
S aureus was effective only on THP-1 cells. When the cell lines were
preincubated with compounds known to induce them to differentiate,
production of tumor necrosis factor alpha (TNF alpha) and IL-1 beta was in
most cases maximal in cells with differentiated characteristics, whereas
NKSF/IL-12 production in response to LPS in all three producing cell lines
was significantly enhanced only by pretreatment with dimethylsulfoxide
(DMSO) for 24 hours, or by costimulation with interferon gamma (IFN gamma).
The efficiency of DMSO enhancement of NKSF/IL-12 production decreased after
2 to 5 days of incubation, when the cells acquired differentiated
characteristics. Unlike DMSO, IFN gamma enhanced NKSF/IL-12 production, and
IL-10 and dexamethasone inhibited it in cell lines and PB mononuclear cells
stimulated by either LPS or S aureus. The ability of the cell lines to
respond to these mediators of possibly physiologically relevant function
provides a tissue-culture model for studying their mechanism of action.
Volume 83,
Issue 7,
pp. 1847-1855,
04/01/1994
Copyright © 1994 by The American Society of Hematology
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