Similarities and differences between the interleukin-1 induction and action pathways in human macrophages.
Cyclic AMP, protein kinase A and NF kappa B have been implicated as second messengers in the interleukin-1 (IL-1) action pathway. Since IL-1 induces more IL-1 release, the IL-1 action pathway may share some common second messengers with the IL-1 induction pathway. Therefore, we investigated whether cyclic AMP, protein kinase A and NF kappa B are involved in the induction of IL-1 beta release by human peripheral blood monocyte-derived macrophages (HPBM) stimulated with a specific IL-1 beta inducer, 9-hydroxyoctadecadienoic acid (9-HODE). With regard to cyclic AMP, it peaked 30 min after 9-HODE stimulation. A role for cyclic AMP in IL-1 beta induction was suggested since forskolin was sufficient to induce IL-1 beta release from HPBM. 9-HODE stimulation of HPBM also activated an early peak of protein kinase A activity. A requirement of protein kinase A in IL-1 beta induction was suggested since 9-HODE-induced IL-1 beta release was inhibited with a selective protein kinase A inhibitor, Rp-isomer (IC50:5 microM). Lastly, to examine the role of NF kappa B, incubation of HPBM with a double-stranded oligodeoxyribonucleotide (ds-oligo) bearing the NF kappa B consensus sequence produced a dose-dependent enhancement of 9-HODE-induced IL-1 beta release, whereas a ds-oligo containing an unrelated Oct-1 motif had no effect. These results suggest that NF kappa B plays a negative role in the IL-1 beta induction pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
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Marion Merrell Dow Research Institute, Cincinnati, Ohio.
Flanagan
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D001483:Base Sequence; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D008041:Linoleic Acids / Q000494:pharmacology; D044243:Linoleic Acids, Conjugated; D008264:Macrophages / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
D007375:Interleukin-1; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; D016328:NF-kappa B; C024347:9-hydroxy-10,12-octadecadienoic acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases