Regulation of monokine gene expression: prostaglandin E2 suppresses tumor necrosis factor but not interleukin-1 alpha or beta-mRNA and cell-associated bioactivity.

Abstract

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