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.
Zhang
Bin
B
School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Western Road, Jinan 250012, China.
Zhang
Jian
J
Tian
Zhigang
Z
D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D053804:Granzymes / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D018664:Interleukin-12 / Q000494:pharmacology*; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000201:enzymology
D016898:Interferon-alpha; D019409:Interleukin-15; D007376:Interleukin-2; D018664:Interleukin-12; D053804:Granzymes