Regulation of interleukin 8 expression in human malignant melanoma cells

Here, we report the molecular regulation of interleukin (IL)-8 expression in human melanoma cells. The inflammatory cytokines IL-1beta and tumor necrosis factor-alpha (TNF-alpha) up-regulated IL-8 expression, in a time- and concentration-dependent manner, in three metastatic melanoma variants, SBC-2 (nonmetastatic), A375P (low metastatic), and A375SM (high metastatic), by increased transcription of the IL-8 gene, leading to increased levels of IL-8 mRNA and protein production. Furthermore, we report that IFN-alpha and IFN-beta did not inhibit steady-state IL-8 production. However, IFN-alpha and IFN-beta inhibited IL-1beta or TNF-alpha-mediated up-regulation of IL-8 mRNA. In addition, IFN-beta demonstrated a more potent inhibitory effect at a lower concentration than did IFN-alpha. Both pretreatment and simultaneous treatment of melanoma cells with IFN-alpha or IFN-beta inhibited the IL-1beta and TNF-alpha up-regulation of IL-8 mRNA levels. This inhibition was at the transcriptional levels and was unaffected by a protein synthesis inhibitor, suggesting that this did not require de novo protein synthesis. Further, modulation of IL-8 levels by IL-1beta, alone or in combination with IFN-beta, affected the proliferation of melanoma cells. In summary, our data suggest that the up-regulation of IL-8 expression in melanoma cells is regulated at the transcriptional level and is rapidly and specifically inhibited by IFN-alpha or IFN-beta, independent of de novo protein synthesis, perhaps due to a transient modification of a preexisting factor(s).