Premium
Regulation of Monokine Gene Expression: Prostaglandin E 2 Suppresses Tumor Necrosis Factor but Not Interleukin‐1α or β‐mRNA and Cell‐Associated Bioactivity
Author(s) -
Scales W.E.,
Chensue S.W.,
Otterness I.,
Kunkel S.L.
Publication year - 1989
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.45.5.416
Subject(s) - monokine , biology , tumor necrosis factor alpha , interleukin , northern blot , prostaglandin e2 , endocrinology , lipopolysaccharide , microbiology and biotechnology , medicine , cytokine , messenger rna , immunology , gene , biochemistry
Prostaglandin E 2 (PGE 2 )‐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 ‐7 M PGE 2 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 PGE 2 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 PGE 2 suppressed TNF, but not IL‐1α or ‐β expression, supporting the bioassay data. These results imply that PGE 2 ‐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.