Regulation of Monokine Gene Expression: Prostaglandin E2 Suppresses Tumor Necrosis Factor but Not Interleukin-1α or β-mRNA and Cell-Associated Bioactivity

Abstract

Abstract Prostaglandin E2 (PGE2)-mediated suppression of macrophage interleukin-1α,β and tumor necrosis factor-α synthesis was examined at the cellular and molecular levels. Treatment of lipopolysaccharide (LPS)-stimulated adjuvant-elicited murine macrophages with 5 × 10-7M PGE2 caused a 70% reduction in cell-associated TNF but had no suppressive effect on cell-associated interleukln-1 (IL-1) activity. Consistent with this result, Northern blot and nuclear transcription analyses demonstrated suppression of TNF mRNA but PGE2 had no effect on IL-1α and IL-1β mRNA accumulation, as compared to LPS controls. Immunoperoxidase staining for cell-associated TNFα, IL-1α, and IL-1β demonstrated that PGE2 suppressed TNF, but not IL-1α or -β expression, supporting the bioassay data. These results imply that PGE2-mediated regulation of IL-1α,β and TNFα is quite distinct. Synthesis of TNF appears to be regulated at least at the level of transcription, whereas that for IL-1α and -β is regulated post-transcriptionally.