title: 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.
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.
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
authors.forename: Seo Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
authors.forename: Keun-Yeong
authors.initials: KY
authors.lastname: Jeong
authors.affiliation: Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
authors.forename: Jinsil
authors.initials: J
authors.lastname: Seong
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000528:radiation effects; D018664:Interleukin-12 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy; D008297:Male; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D020569:Proto-Oncogene Proteins c-rel / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D020569:Proto-Oncogene Proteins c-rel; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D018664:Interleukin-12