IFNalpha regulates NK cell cytotoxicity through STAT1 pathway.
Human natural killer (NK) cell lines (YT and NK-92) and freshly isolated human NK cells were used to determine signal pathway (s) and their cytolysis-related molecules involved in IFNalpha-stimulated natural cytotoxicity. NK cells displayed apparently augmented cytotoxicity against target tumor cells (K562) and up-regulated gene expression of cytolytic effectors Fas-L and perforin in response to IFNalpha stimulation. Meanwhile, the tyrosine phosphorylation of STAT1 of NK cells was quickly induced, but other pathways including STAT3, STAT6, ERK1/2, p38 MAPK, JNK/SAPK, PI-3K, NF-kappaB were not or only weakly activated. Transient expression of dominant-negative form of STAT1 (DN STAT1) markedly inhibited STAT1 activation and then alleviated cytolysis activity of IFNalpha-treated YT cells, which was correlated to a markedly down-regulated expression of IRF-1, a key transcription factor necessary for cytotoxicity of IFNalpha/beta-activated NK cells. The results indicate that STAT1 activation play a crucial role in IFNalpha signaling for cytolysis function of NK cells.
Liang
Shujuan
S
School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei City 230027, Anhui, China.
Wei
Haiming
H
Sun
Rui
R
Tian
Zhigang
Z
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators