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


CONCLUSIONS
From previous results, we summarize our current understanding of the augmentation of distinct regulation of NK cells by IL-27 and IL-12.
Department of Medical Research, Tao-Yuan General Hospital, Taoyuan, Taiwan.
Juei-Chang
JC
Chen
Ai-Ju
AJ
Huang
Shih-Chang
SC
Chen
Jia-Long
JL
Wu
Wen-Mein
WM
Wu
Han-Sun
HS
Chiang
Chia-Hao
CH
Chan
Chih-Ming
CM
Lin
Yu-Tzu
YT
Huang
D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D008213:Lymphocyte Activation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D015415:Biomarkers; D007378:Interleukins; C464565:MYDGF protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D018664:Interleukin-12