TRAIL expression up-regulated by interferon-gamma via phosphorylation of STAT1 induces myeloma cell death

Although the cellular and molecular biological effects of interferon (IFN)-alpha have been well-investigated, the effects of IFN-gamma are less understood. Eleven human myeloma cell lines with various myeloma-specific chromosomal translocations and overexpression of oncogenes were cultured with 1000 U/ml of IFN-gamma. In the KMS-20 cells, which showed growth inhibition due to IFN-gamma, trail expression, status of the Janus kinase (JAK)/STAT pathway were analyzed. KMS-20 cells showed marked up-regulation of trail, activation of STAT1 and TRAIL hyperproduction induced by IFN-gamma. The effects of IFN-gamma on growth inhibition of KMS-20 cells were characterized by activation of the JAK/STAT signalling pathway, particularly STAT1 phosphorylation, enhanced secretion of TRAIL, and auto/paracrine usage of secreted TRAIL to induce apoptotic cell death. From these results, IFN-gamma may be considered one of the drugs to be used in future multidrug chemotherapeutic regimens for myeloma patients.