Tumor-derived products induce Il-1 a, Il-1 b, Tnf a, and Il-6 gene expression in murine macrophages: distinctions between tumor- and bacterial endotoxin-induced gene expression.
The ability of progressing tumors to regulate host physiology is an important consideration in our understanding of tumor-host relationships. Previous data indicated that several lines of murine sarcoma cells produced one or more activities that were able to regulate both Il-1 a and Il-1 b gene transcription in macrophages (MO). We now describe an indepth analysis using Northern analysis and bioassays and show that two of these tumors produce one or more activities that when incubated with peritoneal MO result in the transcription of the Il-1a, Il-1 b, Tnf a, and Il-6 genes. Concordant with the Northern analyses was the finding that interleukin-1 (IL-1) and tumor necrosis factor (TNF) biological activities were detected in lysates of induced MO, fixed MO, and supernates of MO cultures. Induction of gene expression was shown to be distinct from that induced by bacterial endotoxin or lipopolysaccharide by a number of criteria. The data suggest that tumor cell products may play an important role in regulating several host physiological processes, particularly those involving Il-1a, Il-1 b, Tnf a, and Il-6 gene expression.
Evans
R
R
Jackson Laboratory, Bar Harbor, ME 04609.
Kamdar
S J
SJ
Duffy
T M
TM
D000818:Animals; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D015870:Gene Expression / Q000187:drug effects; D007375:Interleukin-1 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D046911:Macromolecular Substances; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D012513:Sarcoma, Experimental / Q000503:physiopathology*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha