Defective lipopolysaccharide-induced production of both interleukin 1 alpha and interleukin 1 beta by A/J mouse macrophages is posttranscriptionally regulated.
Interleukin 1 (IL-1) production by A/J (A) and C57BL/6J (B6) mouse peritoneal macrophages stimulated with lipopolysaccharide (LPS) was determined. Strain A macrophages produced low levels of soluble IL-1 bioactivity compared with B6 macrophages. This defect was not reversed by indomethacin, interferon-gamma, phorbol myristate acetate, or calcium ionophore A23187. In contrast, cytosolic IL-1 bioactivity was similar in LPS-stimulated A and B6 macrophages. Western blotting revealed that A macrophage supernatants contained lower levels of both 17-kd IL-1 alpha and 17-kd IL-1 beta but similar levels of tumor necrosis factor alpha compared with B6 macrophages. Cytosolic levels of 31-kd pro-IL-1 alpha and also 31-kd pro-IL-1 beta were similar in A and B6 macrophages. Oligonucleotide probing indicated that A and B6 macrophages contained similar levels of IL-1 alpha and also IL-1 beta mRNA. These findings indicate that LPS-stimulated A macrophage culture supernatants contain low levels of both IL-1 alpha and IL-1 beta compared with B6 macrophages and that these defects in IL-1 production are posttranscriptionally regulated.
Brandwein
S R
SR
Department of Medicine, McGill University, Montreal, Canada.
Maenz
L
L
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin