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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.

 Eun-Jung Lee  ;  Seo Jin Lee  ;  Ji-Hye Kim  ;  Kyoung-Jin Kim  ;  Seung-Hyun Yang  ;  Keun Yeong Jeong  ;  Jinsil Seong 
 PLOS ONE, Vol.11(1) : e0146463, 2016 
Journal Title
Issue Date
Animals ; Carcinoma, Hepatocellular/immunology ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/radiotherapy ; Cell Line, Tumor ; Dendritic Cells/immunology ; Dendritic Cells/metabolism* ; Dendritic Cells/radiation effects ; Interleukin-12/biosynthesis* ; Interleukin-6/physiology* ; Lipopolysaccharides/pharmacology ; Liver Neoplasms, Experimental/immunology ; Liver Neoplasms, Experimental/metabolism ; Liver Neoplasms, Experimental/radiotherapy ; Male ; Mice, Inbred C3H ; Neoplasm Transplantation ; Proto-Oncogene Proteins c-rel/physiology* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction
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.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
Lee, Eun Jung(이은정)
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