Regulation of Interleukin-8 Gene Expression by All-transRetinoic Acid

We have studied the relationship between interleukin-8 (IL-8) and interleukin-1α (IL-1α) release after stimulation with all-transretinoic acid (ATRA) and tumor necrosis factor-α (TNF-α) in the human epithelial ovarian cancer cell line HOC-7. Both IL-1α and IL-8 protein release were enhanced by treatment with ATRA and TNF-α after 48 h exposure. Blocking of IL-1α activity in HOC-7 cells with either IL-1 receptor antagonist (IL-1ra) or a neutralizing antibody directed against IL-1α resulted in a dose-dependent decrease of IL-8 release by ATRA, TNF-α and IL-1α treated HOC-7 cells. Expression of IL-8 mRNA was enhanced by the individual stimuli, whereas cotreatment with IL-lra resulted in a loss of IL-8 specific transcripts, except in TNF-α treated cells. Inhibition of de novoprotein synthesis by cycloheximide (CHX) and simultaneous blocking of IL-1α activity by IL-1ra for 24 h revealed that ATRA controls IL-8 gene expression transcriptionally and that the extent of IL-8 protein release can be markedly influenced by cellular expressed IL-1α.