DEFECTIVE LIPOPOLYSACCHARIDE-INDUCED PRODUCTION OF BOTH INTERLEUKIN-1-ALPHA AND INTERLEUKIN-1-ALPHA 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-1alpha and 17-kd IL-1beta but similar levels of tumor necrosis factor alpha compared with B6 macrophages. Cytosolic levels of 31-kd pro-IL-1alpha and also 31-kd pro-IL-1beta were similar in A and B6 macrophages. Oligonucleotide probing indicated that A and B6 macrophages contained similar levels of IL-1alpha and also IL-1beta mRNA. These findings indicate that LPS-stimulated A macrophage culture supernatants contain low levels of both IL-1alpha and IL-1beta compared with B6 macrophages and that these defects in IL-1 production are posttranscriptionally regulated.