Inhibition of the arachidonic acid pathway prevents induction of IL-8 mRNA by phorbol ester and changes the release of IL-8 from HL 60 cells: differential inhibition of induced expression of IL-8, TNF-alpha, IL-1 alpha, and IL-1 beta.

摘要: The promyelocytic HL 60 cell line can be used as an in vitro model system to study hematopoetic differentiation and inflammatory events. We studied the signal transduction pathway of induced interleukin (IL)-8 expression compared it with those tumor necrosis factor alpha (TNF-alpha), IL-1 alpha, beta. cells macrophage-like by PMA resulted a rapid marked induction these cytokines. up-regulation occurred absence ongoing protein synthesis, but cycloheximide-sensitive gene products modulated their kinetics. Staurosporine, potent inhibitor kinases, strongly inhibited expression. Phosphorylation may not act directly on latent transcription factors, since bromophenacyl bromide, for release arachidonic acid from phorbol-12 myristate 13-acetate (PMA)-stimulated cells, markedly depressed mRNAs IL-8, TNF-alpha, -beta. Similarly, 5,8,11,14 eicosatetraynoic (ETYA), another pathway, blocked transcripts both genes phorbol ester-stimulated cells. In contrast, ETYA increased IL-8 RNA levels stimulated IL-8. Also, ketoconazole, 5-lipoxygenase indomethacin, cyclooxygenases did block mRNA. However, was regulated indomethacin ketoconazole. Our results indicate that metabolites are mediators involved second messengers different which important TNF-alpha beta