Interleukin-27 and interleukin-12 augment activation of distinct cord blood natural killer cells responses via STAT3 pathways

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• 作者：Juei-Chang Chen^a ; ^&dagger ; ; Ai-Ju Huang^b ; ^&dagger ; ; Shih-Chang Chen^c ; Jia-Long Wu^b ; Wen-Mein Wu^d ; Han-Sun Chiang^b ; Chia-Hao Chan^b ; Chih-Ming Lin^e ; Yu-Tzu Huang^b ; ^{med0043@mail.fju.edu.tw}
• 关键词：cord blood ; interleukin-27 ; interleukin-12 ; glycoprotein-130 ; natural killer cells ; STAT3
• 刊名：Journal of the Formosan Medical Association
• 出版年：2012
• 期刊代码：211_09296646
• 类别：med
• 出版时间：May, 2012
• 卷：111
• 期：5
• 页码：275-283
• 文件大小：787 K

摘要

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Background/Purpose

Umbilical cord blood is rich in primitive natural killer (NK) cells, which are activated by interleukin (IL)-12. It was previously reported that a novel IL-12 family cytokine, IL-27 comprised of EBI3 and p28, was elevated in maternal serum during normal pregnancy. Thus, we compared the immune regulatory functions of IL-27 and IL-12 on mononuclear cells derived from cord blood and adult peripheral blood.

Methods

After stimulation with IL-27, IL-12, and IL-27 combined with IL-12, the cytotoxicity against BJAB lymphoma cells by blood mononuclear cells was performed. Then immunofluorescence staining, reverse transcriptase-polymerase chain reaction and Western blotting were used to detect the effects of IL-27 and IL-12 in isolated NK cells.

Results

IL-27, IL-12, and IL-27 combined with IL-12 enhanced the cytotoxicity of adult peripheral blood cells and cord blood cells, but the proliferation of distinct subpopulations of cells was not evident. Similar results were also obtained with purified cord blood NK cells. Interestingly, distinct from IL-12, IL-27 could induce aggregation and morphological changes of umbilical cord blood cells. Finally, IL-27 combined with IL-12 could stimulate increased IL-27 receptor (gp130 and WSX-1) transcripts in purified cord blood NK cells. However, the activation of signal transducer and activator of transcription 3 (STAT3) in NK cells was only detected in the presence of IL-27, but not IL-12 alone.

Conclusion

From previous results, we summarize our current understanding of the augmentation of distinct regulation of NK cells by IL-27 and IL-12.