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  • [PLoS One] Radiation Inhibits Interleukin-12 Production via Inhibition of C-Rel through the Interleukin-6/ Signal Transducer and Activator of Transcription 3 Signaling Pathway in Dendritic Cells.

    연세의대 / 이은정,성진실*

  • 출처
    PLoS One
  • 등재일
    2016 Jan 8
  • 저널이슈번호
    11(1):e0146463. doi: 10.1371/journal.pone.0146463. eCollection 2016.
  • 내용

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    Abstract

    Radiotherapy (RT) is a potent anti-tumor modality. However, unwanted effects including increased recurrence and metastasis that involve factors such as cytokines, which induce complex molecular mechanisms, have also been reported. In a previous study, we showed that interleukin (IL)-12 and radiotherapy combination treatment suppressed tumor growth and metastasis in a hepatoma mouse model. In this study, we investigated the mechanism underlying the IL-12 anti-tumor effect during radiotherapy. In tumor-bearing mice, irradiation decreased IL-12 expression in the tumors and spleens. However, a number of dendritic cells infiltrated into the tumors in which IL-12 expression did not decrease. To further study the underlying detailed mechanism for this decrease in IL-12, LPS-stimulated bone marrow-derived dendritic cells (BMDCs) were irradiated, and then IL-12- and IL-6-associated molecules were examined in irradiated tumors and BMDCs. Irradiation resulted in IL-12 suppression and IL-6 increase. IL-6 and signal transducer and activator of transcription 3 (STAT3) inhibitors restored the irradiation-induced IL-12 decrease via suppression of C-Rel activation. Taken together, our study suggests that irradiation-induced IL-6 can decrease IL-12 production through the inhibition of C-Rel phosphorylation by the IL-6/STAT3 signaling pathway. 

     

     

    Author information

    Lee EJ1, Lee SJ1, Kim JH1, Kim KJ1, Yang SH1, Jeong KY1, Seong J1.

    1 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.  

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