Comparison in the effects of IL-2, IL-12, IL-15 and IFNalpha on gene regulation of granzymes of human NK cell line NK-92.

Serine protease granzymes (GZM) are key effector molecules of granule-mediated cytotoxicity of NK cell, but the requirement for their expression regulation remains largely undefined. In this study, it was showed that IL-2, IL-12, IL-15 and IFNalpha differently regulated the expression of granzymes in NK cells. Although IL-2, IL-12, IL-15 and IFNalpha exerted overlapping positive effects on transcripts of GZM-A and GZM-B, the augment extent and the peaked time course were different for each GZM member after stimulation with these cytokines. Additionally, only IFNalpha up-regulated the transcription of GZM-K, while IL-15 dramatically down-regulated the GZM-H mRNA level. The protein levels of GZM-B and cytotoxicity of NK-92 cells in response to IL-2 or IFNalpha were analyzed, the results showed a positive relationship between cytotoxicity and GZM-B expression level. Together, these findings illustrated that IL-2, IL-12, IL-15 and IFNalpha exerted differential regulating effects on granzyme genes of NK cells.