IL-12 reverses inhibitory effect of cisplatin on immune function of human NK cells and its mechanism
10.3872/j.issn.1007-385x.2018.09.005
- VernacularTitle:IL-12逆转顺铂对人NK细胞免疫功能的抑制及其机制
- Author:
SHEN Juan
1
;
WU Qiongli
1
;
YANG Binyan
1
;
WU Changyou
1
Author Information
1. Institute of Immunology, Key Laboratory of Organ Donation and Transplant Immunology of Guangdong Provincial, Zhongshan School of Medicine, Sun Yat-sen University
- Publication Type:Journal Article
- Keywords:
NK cell;
DDP;
IL-12;
immune suppression;
Jurkat cell line
- From:
Chinese Journal of Cancer Biotherapy
2018;25(9):872-877
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the reverse effect and mechanism of IL-12 on chemotherapeutic medicine suppressing the immune function of NK cells. Methods: Purified NK cells were stimulated with PMAplus Ionomycin in the presence or absent of Cisplatin (DDP) and IL-12. The levels of IFN-γ and TNF-α in culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA); The content of IFN-γ and TNF-α, TRAIL (TNF-related apoptosis inducing ligand) and transcription factors including T-bet and p-STAT-4 in NK cells were analyzed by Flow cytometry. The cytotoxicity of purified NK cells (pretreated with/without chemotherapeutics and IL-12 for 48 h) to Jurkat cells was measured by Flow cytometry. Results: Chemotherapeutics significantly inhibited the production of IFN-γ, TNF-α and the expression of TRAILin NK cells, which were significantly reversed by IL-12 (P<0.05 or P<0.01). Further study revealed that chemotherapeutics down-regulated while IL-12 reversed the expression of p-STAT4 to restore cytokine production. In addition, DDP also inhibited but IL-12 recovered the cytotoxicity of NK cells against tumor cells by inducing the expression of TRAIL (P<0.05 or P<0.01). Conclusion: Chemotherapeutics inhibited the cytotoxicity of NK cells and its secretion of cytokines (IFNγ and TNF-α), which were reversed by IL-12 via up-regulating TRAIL and p-STAT-4; this might provide experimental evidence for the clinical application of IL-12 for rebuild the immune function of tumor patients receiving chemotherapy.
- Full text:20180905.pdf
