Wachanan Wongsena1, Lakhanawan Charoensuk2, Rungtiwa Dangtakot3, Porntip Pinlaor3, Kitti Intuyod4, Somchai Pinlaor5. 1. Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Thailand. 2. Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Thailand. 3. Center of Research and Development in Medical Diagnostic Laboratory, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Thailand. 4. Biomedical Science Program, Graduate School, Khon Kaen University, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Thailand. 5. Department of Parasitology, Faculty of Medicine, Khon Kaen University, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Thailand. Electronic address: psomec@kku.ac.th.
Abstract
BACKGROUND: The combination of Opisthorchis viverrini (OV) infection and chemical carcinogen induces cholangiocarcinoma (CCA) in hamsters via inflammation-mediated mechanisms. Thus, suppression of inflammatory cells at the initial stages of CCA development would be of benefit. We aimed to investigate whether IL-17-producing CD4+ T cells (Th17) and CD4+ Foxp3+ T cells (Treg) are involved in the early stages of CCA genesis and can be targeted for suppression by melatonin. METHODS: Inflammation, an initial stage of CCA development, was induced in hamsters by a combination of O. viverrini infection and N-nitrosodimethylamine (NDMA) administration. Melatonin (50mg/kg) was additionally administered to one group for the 30days of the experiment. Liver tissue-resident T cells were investigated using immunostaining, western blotting, and real-time PCR. RESULTS: OV+NDMA-induced CCA tissues showed significantly higher numbers of inflammatory cells, especially eosinophils, bile duct proliferation and IL-17+ cell infiltration compared to normal livers. Expression of Foxp3 was localized in the bile duct epithelial cells, and especially in the bile duct hyperplasia. Accumulation of CD4+ and IL-17+ cells and intense staining of the Foxp3+ marker were consistent with their protein levels. Infiltration of IL-17+ inflammatory cells and Foxp3+ cells, as well as increases in their transcription expression levels, were significantly lower in the melatonin-treated group. In contrast, increased CD4+ cell infiltration and TNF-α expression were also observed through melatonin treatment. CONCLUSION: Melatonin exerts an immunomodulatory effect, suppressing eosinophils and Th17 cells and expression of Foxp3, but enhancing CD4+ cells and TNF-α. This suggests that melatonin may be used for CCA chemoprevention.
BACKGROUND: The combination of Opisthorchis viverrini (OV) infection and chemical carcinogen induces cholangiocarcinoma (CCA) in hamsters via inflammation-mediated mechanisms. Thus, suppression of inflammatory cells at the initial stages of CCA development would be of benefit. We aimed to investigate whether IL-17-producing CD4+ T cells (Th17) and CD4+ Foxp3+ T cells (Treg) are involved in the early stages of CCA genesis and can be targeted for suppression by melatonin. METHODS:Inflammation, an initial stage of CCA development, was induced in hamsters by a combination of O. viverriniinfection and N-nitrosodimethylamine (NDMA) administration. Melatonin (50mg/kg) was additionally administered to one group for the 30days of the experiment. Liver tissue-resident T cells were investigated using immunostaining, western blotting, and real-time PCR. RESULTS:OV+NDMA-induced CCA tissues showed significantly higher numbers of inflammatory cells, especially eosinophils, bile duct proliferation and IL-17+ cell infiltration compared to normal livers. Expression of Foxp3 was localized in the bile duct epithelial cells, and especially in the bile duct hyperplasia. Accumulation of CD4+ and IL-17+ cells and intense staining of the Foxp3+ marker were consistent with their protein levels. Infiltration of IL-17+ inflammatory cells and Foxp3+ cells, as well as increases in their transcription expression levels, were significantly lower in the melatonin-treated group. In contrast, increased CD4+ cell infiltration and TNF-α expression were also observed through melatonin treatment. CONCLUSION:Melatonin exerts an immunomodulatory effect, suppressing eosinophils and Th17 cells and expression of Foxp3, but enhancing CD4+ cells and TNF-α. This suggests that melatonin may be used for CCA chemoprevention.
Authors: Paula Fernández-Palanca; Carolina Méndez-Blanco; Flavia Fondevila; María J Tuñón; Russel J Reiter; José L Mauriz; Javier González-Gallego Journal: Antioxidants (Basel) Date: 2021-01-12
Authors: Oscar K Bitzer-Quintero; Genaro G Ortiz; Socorro Jaramillo-Bueno; Elsy J Ramos-González; María G Márquez-Rosales; Daniela L C Delgado-Lara; Erandis D Torres-Sánchez; Aldo R Tejeda-Martínez; Javier Ramirez-Jirano Journal: Molecules Date: 2022-07-30 Impact factor: 4.927