title: HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses in fractionated γ-irradiated mice by modulating the IL-12p70-STAT4 signaling pathway.
abstract: Whole body irradiated mice appear to experience a down-regulation of the helper T (Th)1-like immune response, and maintain a persistent immunological imbalance. In the current study, we evaluated the effect of HemoHIM (an herbal product made from Angelica Radix,  Cnidium officinale , and  Paeonia japonica  cultivated in Korea) to ameliorate the immunological imbalance induce in fractionated γ-irradiated mice. The mice were exposed to γ rays twice a week (0.5 Gy fractions) for a total dose of 5 Gy, and HemoHIM was administrated orally from 1 week before the first irradiation to 1 week before the final analysis. All experiments were performed 4 and 6 months after their first exposure. HemoHIM ameliorated the Th1- and Th2-related immune responses normally occur in irradiated mice with or without dinitrophenylated keyhole limpet hemocyanin immunization. HemoHIM also restored the natural killer cell activities without changing the percentage of natural killer cells in irradiated mice. Furthermore, the administration of HemoHIM prevented the reduction in levels of interleukin-12p70 in irradiated mice. Finally, we found that HemoHIM enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 4 that was reduced in irradiated mice. Our findings suggest that HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses by modulating the IL-12p70/pSTAT4 signaling pathway.
authors.affiliation: Radiation Research Division for Bio-Technology, Jeongeup Campus of Korea Atomic Energy Research Institute (KAERI), 1266 Sinjeong-dong Jeongeup-si Jeonbuk 580-185, Republic of Korea.
authors.forename: Hae-Ran
authors.initials: HR
authors.lastname: Park
authors.forename: Sung-Kee
authors.initials: SK
authors.lastname: Jo
authors.forename: Nam-Hee
authors.initials: NH
authors.lastname: Choi
authors.forename: Uhee
authors.initials: U
authors.lastname: Jung
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000528:radiation effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D007114:Immunization; D007153:Immunologic Deficiency Syndromes / Q000209:etiology / Q000517:prevention & control*; D018664:Interleukin-12 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000276:immunology; D011837:Radiation-Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050797:STAT4 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: C529537:HemoHIM; D008222:Lymphokines; D010936:Plant Extracts; D011837:Radiation-Protective Agents; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D018664:Interleukin-12