PMID- 36423715 OWN - NLM STAT- MEDLINE DCOM- 20221220 LR - 20221221 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 373 DP - 2023 Jan 15 TI - Effect of trichloroethanol on TLR2 and TLR4/NF-kappaB-mediated antigen processing and presentation in HLA-B* 13:01-transfected antigen-presenting cells. PG - 123-131 LID - S0378-4274(22)01793-3 [pii] LID - 10.1016/j.toxlet.2022.11.009 [doi] AB - Trichloroethanol (TCOH), as a metabolite of trichloroethylene, has sensitization in the pathogenesis of trichloroethylene-induced hypersensitivity dermatitis (TIHD) which the human leukocyte antigen (HLA)-B *13:01 gene is strongly associated with it. However, it is still obscure how TCOH participates in the pathogenesis of TIHD. Here, we demonstrate that TLR2 and TLR4 signaling through MyD88 and TRAF6-dependent pathway could activate NF-kappaB by promoting degradation of the inhibitor IkappaB-alpha to stimulate the process of NF-kappaB nuclear translocation. Besides, the crucial molecules of antigen processing and presentation, including TAP1, LMP2, LMP7, and HLA-B* 13:01, were all enhanced and the abundance of HLA-B* 13:01 on the surface of CIR-B* 13:01 cells was also up-regulated with the TCOH concentration increasing. Notably, we used 50 muM pyrrolidinedithiocarbamate (ammonium) to effectively inhibit the activation of NF-kappaB, which could effectively reverse the stimulation of antigen processing and presentation in TCOH-treated CIR-B* 13:01 cells. Taken together, we speculated that TCOH could promote the abundance of HLA complex on the antigen-presenting cells via TLR2 and TLR4/NF-kappaB to induce the severe reactivation of T lymphocytes, leading to the extreme immune response. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Yi, Mengnan AU - Yi M AD - Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. FAU - Liu, Shuai AU - Liu S AD - Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. FAU - Jiao, Bo AU - Jiao B AD - Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. FAU - Niu, Yong AU - Niu Y AD - Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. FAU - Shen, Meili AU - Shen M AD - Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. FAU - Duan, Huawei AU - Duan H AD - Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. FAU - Dai, Yufei AU - Dai Y AD - Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. Electronic address: daiyf@niohp.chinacdc.cn. LA - eng PT - Journal Article DEP - 20221121 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (NF-kappa B) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - AW835AJ62N (2,2,2-trichloroethanol) RN - 290YE8AR51 (Trichloroethylene) RN - 0 (HLA-B Antigens) RN - 0 (TLR2 protein, human) RN - 0 (TLR4 protein, human) SB - IM MH - Humans MH - *NF-kappa B/metabolism MH - Toll-Like Receptor 2/genetics/metabolism MH - Toll-Like Receptor 4/genetics/metabolism MH - Antigen Presentation MH - *Trichloroethylene MH - Antigen-Presenting Cells/metabolism MH - HLA-B Antigens OTO - NOTNLM OT - Antigen processing and presentation OT - HLA-B* 13:01 OT - TIHD OT - TLRs/NF-kappaB OT - Trichloroethanol COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/11/25 06:00 MHDA- 2022/12/21 06:00 CRDT- 2022/11/24 19:24 PHST- 2022/07/04 00:00 [received] PHST- 2022/10/28 00:00 [revised] PHST- 2022/11/17 00:00 [accepted] PHST- 2022/11/25 06:00 [pubmed] PHST- 2022/12/21 06:00 [medline] PHST- 2022/11/24 19:24 [entrez] AID - S0378-4274(22)01793-3 [pii] AID - 10.1016/j.toxlet.2022.11.009 [doi] PST - ppublish SO - Toxicol Lett. 2023 Jan 15;373:123-131. doi: 10.1016/j.toxlet.2022.11.009. Epub 2022 Nov 21.