Secretion of interleukin-1 beta by a leukemia cell line in response to lipopolysaccharide and mezerein.
The acute monocytic leukemia cell line, THP-1, is frequently used as a model to study the mechanism of cell-mediated immune response. The model is justified, in part, because THP-1 cells can be induced to express features of activated peripheral blood monocytes or tissue macrophages. The current investigation, however, demonstrates that THP-1 cells differ from normal monocytes in their secretion of interleukin-1 beta (IL-1 beta) following exposure to reagents that induce synthesis. For example, LPS treatment alone did not result in IL-1 beta secretion and very low concentrations were observed when lipopolysaccharide (LPS)-treated cells were simultaneously incubated with silica or silica in combination with hydroxyurea. Silica-enhanced release of IL-1 was related to changes in cell membrane permeability. Recombinant interferon-gamma (rIFN gamma) alone did not induce IL-1 beta secretion and did not significantly increase secretion by LPS- and silica-stimulated cells. In contrast, mezerein stimulation led to higher extracellular concentrations of IL-1 beta and rIFN gamma augmented secretion by mezerein-treated cells. Isoelectrofocusing of conditioned medium and titration of pooled fractions showed a direct correlation between extracellular levels of biologically active and immunoreactive IL-1. The role of IFN gamma in stimulating IL-1 beta secretion was not related to an enhancement of viability or an increase in the proportion of mezerein-treated cells synthesizing DNA. It was concluded that mezerein's regulation of secretion by THP-1 cells depended on the expression of monocyte features, including cell adherence and responsiveness to IFN gamma.
Gaffney
E V
EV
Department of Research, Baptist Medical Centers, Birmingham, Alabama 35213.
Stoner
C R
CR
Lingenfelter
S E
SE
Koch
G A
GA
D000818:Animals; D001681:Biological Assay; D002455:Cell Division; D002470:Cell Survival; D004224:Diterpenes; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D007525:Isoelectric Focusing; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins; D013729:Terpenes / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology; D014407:Tumor Cells, Cultured
D004224:Diterpenes; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D013729:Terpenes; C011309:mezerein; D007371:Interferon-gamma