PMID- 32679628 OWN - NLM STAT- MEDLINE DCOM- 20200729 LR - 20200729 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 255 DP - 2020 Sep TI - Decrease in immune function and the role of mitogen-activated protein kinase (MAPK) overactivation in apoptosis during T lymphocytes activation induced by zearalenone, deoxynivalenol, and their combinations. PG - 126999 LID - S0045-6535(20)31192-9 [pii] LID - 10.1016/j.chemosphere.2020.126999 [doi] AB - Currently there are few reports on the combined immunotoxicity of zearaleone (ZEA) and deoxynivalenol (DON). Since the two coexist naturally, it is necessary to understand the immunotoxicity caused by the two mycotoxins alone and in combination. To examine T lymphocytes activation and immune effect during activation, we used mouse primary spleen T lymphocytes as the experimental material and concanavalin (Con A) as the stimulator. The effects of ZEA, DON, and their combined exposure on T lymphocytes immune related function and the relationship between the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and mycotoxin induced T lymphocytes apoptosis were studied in vitro. Specifically, T lymphocytes were isolated from primary mouse splenic lymphocytes, activated by Con A and then exposed to different concentrations of ZEA, DON, and their combinations. Our results showed that ZEA and DON alone and their combinations (20:1) can decrease the cell viability of T lymphocytes activated by Con A. The inhibitory effect of the combined groups was greater than that of the single mycotoxins, showing a synergistic effect. In addition, single or combined mycotoxins can lead to intracellular and surface ultrastructure damage of T lymphocytes, inhibit the expression of CD25 and CD278 and inhibit the synthesis of effect molecules poreforming protein (PFP), granzyme A (GZMA), and tumor necrosis factor-alpha (TNF-alpha). Meanwhile, the single mycotoxin or combined mycotoxins can promote the apoptosis of T lymphocytes which was accompanied by the overactivation of MAPK. After using the inhibitors of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase (JNK) in the MAPK pathway, we found that the apoptosis of the cells induced by the ZEA was significantly decreased, and the apoptosis of the cells induced by DON had no significant changes. This suggests that the activation of MAPK induced by ZEA can promote the apoptosis of T lymphocytes, but the activation of MAPK induced by DON is not directly related to T cell apoptosis. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Cai, Guodong AU - Cai G AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Sun, Kai AU - Sun K AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. FAU - Xia, Sugan AU - Xia S AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. FAU - Feng, Zhiheng AU - Feng Z AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. FAU - Zou, Hui AU - Zou H AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. FAU - Gu, Jianhong AU - Gu J AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. FAU - Yuan, Yan AU - Yuan Y AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. FAU - Zhu, JiaQiao AU - Zhu J AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. FAU - Liu, Zongping AU - Liu Z AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Bian, Jianchun AU - Bian J AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, China. Electronic address: jcbian@yzu.edu.cn. LA - eng PT - Journal Article DEP - 20200510 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 RN - 0 (IL2RA protein, human) RN - 0 (Immunotoxins) RN - 0 (Interleukin-2 Receptor alpha Subunit) RN - 0 (Mycotoxins) RN - 0 (Trichothecenes) RN - 0 (Tumor Necrosis Factor-alpha) RN - 5W827M159J (Zearalenone) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - JT37HYP23V (deoxynivalenol) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Cell Survival/drug effects MH - Immunotoxins/*toxicity MH - Interleukin-2 Receptor alpha Subunit MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Mice MH - Mitogen-Activated Protein Kinases/*metabolism MH - Mycotoxins/toxicity MH - Signal Transduction MH - T-Lymphocytes/immunology/metabolism MH - Trichothecenes/*toxicity MH - Tumor Necrosis Factor-alpha MH - Zearalenone/*toxicity OTO - NOTNLM OT - Combined mycotoxins OT - Deoxynivalenol OT - Immunotoxicity OT - MAPK OT - T lymphocyte apoptosis OT - Zearalenone COIS- Declaration of competing interest The authors declare no conflict of interest. EDAT- 2020/07/19 06:00 MHDA- 2020/07/30 06:00 CRDT- 2020/07/19 06:00 PHST- 2019/10/09 00:00 [received] PHST- 2020/04/29 00:00 [revised] PHST- 2020/05/05 00:00 [accepted] PHST- 2020/07/19 06:00 [entrez] PHST- 2020/07/19 06:00 [pubmed] PHST- 2020/07/30 06:00 [medline] AID - S0045-6535(20)31192-9 [pii] AID - 10.1016/j.chemosphere.2020.126999 [doi] PST - ppublish SO - Chemosphere. 2020 Sep;255:126999. doi: 10.1016/j.chemosphere.2020.126999. Epub 2020 May 10.