PMID- 27473013 OWN - NLM STAT- MEDLINE DCOM- 20170523 LR - 20180104 IS - 1096-0333 (Electronic) IS - 0041-008X (Linking) VI - 307 DP - 2016 Sep 15 TI - Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay. PG - 72-80 LID - S0041-008X(16)30211-3 [pii] LID - 10.1016/j.taap.2016.07.019 [doi] AB - Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-beta activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-gamma producing CD8(+) T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-gamma production. This effect may occur through Jnk and NF-kappaB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Yao, Pan AU - Yao P AD - Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China. FAU - Hongqian, Chu AU - Hongqian C AD - Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China. FAU - Qinghe, Meng AU - Qinghe M AD - Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China. FAU - Lanqin, Shang AU - Lanqin S AD - Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China. FAU - Jianjun, Jiang AU - Jianjun J AD - Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China. FAU - Xiaohua, Yang AU - Xiaohua Y AD - Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China. FAU - Xuetao, Wei AU - Xuetao W AD - Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China. FAU - Weidong, Hao AU - Weidong H AD - Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China. Electronic address: whao@bjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160727 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (NF-kappa B) RN - 290YE8AR51 (Trichloroethylene) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinases) RN - EC 2.7.11.25 (MAP kinase kinase kinase 7) SB - IM MH - Animals MH - Dendritic Cells/*metabolism MH - Dermatitis, Contact/*genetics/metabolism MH - Female MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Local Lymph Node Assay MH - MAP Kinase Kinase Kinases/*genetics MH - Mice, Transgenic MH - NF-kappa B/metabolism MH - Trichloroethylene MH - p38 Mitogen-Activated Protein Kinases/metabolism OTO - NOTNLM OT - Contact hypersensitivity OT - Dendritic cells OT - Local lymph node assay OT - Transforming growth factor-beta activated kinase-1 OT - Trichloroethylene EDAT- 2016/07/31 06:00 MHDA- 2017/05/24 06:00 CRDT- 2016/07/31 06:00 PHST- 2016/05/23 00:00 [received] PHST- 2016/07/19 00:00 [revised] PHST- 2016/07/25 00:00 [accepted] PHST- 2016/07/31 06:00 [entrez] PHST- 2016/07/31 06:00 [pubmed] PHST- 2017/05/24 06:00 [medline] AID - S0041-008X(16)30211-3 [pii] AID - 10.1016/j.taap.2016.07.019 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2016 Sep 15;307:72-80. doi: 10.1016/j.taap.2016.07.019. Epub 2016 Jul 27.