A. Janssen, Wendy Jansen Holleboom, D. Rijkers, J. Louisse, Sjoerdtje A. Hoekstra, Sanne Schild, M. Vrolijk, Ron L. A. P. Hoogenboom, Karsten Beekmann
{"title":"测定一系列全氟烷基物质(PFAS)在人 Namalwa B 淋巴细胞和人 Jurkat T 淋巴细胞中的体外免疫毒性效力","authors":"A. Janssen, Wendy Jansen Holleboom, D. Rijkers, J. Louisse, Sjoerdtje A. Hoekstra, Sanne Schild, M. Vrolijk, Ron L. A. P. Hoogenboom, Karsten Beekmann","doi":"10.3389/ftox.2024.1347965","DOIUrl":null,"url":null,"abstract":"Exposure to PFASs is associated to several adverse health effects, such as immunotoxicity. Immunotoxic effects of PFOA and PFOS, including a reduced antibody response in both experimental animals and humans, have been reported. However, there is limited understanding of the underlying mechanisms involved. Moreover, there is only a restricted amount of immunotoxicity data available for a limited number of PFASs. In the current study the effects of 15 PFASs, including short- and long-chain perfluorinated carboxylic and sulfonic acids, fluorotelomer alcohols, and perfluoralkyl ether carboxylic acids were studied on the expression of recombinant activating gene 1 (RAG1) and RAG2 in the Namalwa human B lymphoma cell line, and on the human IL-2 promotor activity in Jurkat T-cells. Concentration-response data were subsequently used to derive in vitro relative potencies through benchmark dose analysis. In vitro relative potency factors (RPFs) were obtained for 6 and 9 PFASs based on their effect on RAG1 and RAG2 gene expression in Namalwa B-cells, respectively, and for 10 PFASs based on their inhibitory effect on IL-2 promotor activity in Jurkat T-cells. The most potent substances were HFPO-TA for the reduction of RAG1 and RAG2 gene expression in Namalwa cells (RPFs of 2.1 and 2.3 respectively), and PFDA on IL-2 promoter activity (RPF of 9.1). RAG1 and RAG2 play a crucial role in V (D)J gene recombination, a process for acquiring a varied array of antibodies crucial for antigen recognition. Hence, the effects observed in Namalwa cells might indicate a PFAS-induced impairment of generating a diverse range of B-cells essential for antigen recognition. The observed outcomes in the Jurkat T-cells suggest a possible PFAS-induced reduction of T-cell activation, which may contribute to a decline in the T-cell dependent antibody response. Altogether, the present study provides potential mechanistic insights into the reported PFAS-induced decreased antibody response. Additionally, the presented in vitro models may represent useful tools for assessing the immunotoxic potential of PFASs and prioritization for further risk assessment.","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":"7 5","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Determination of in vitro immunotoxic potencies of a series of perfluoralkylsubstances (PFASs) in human Namalwa B lymphocyte and human Jurkat T lymphocyte cells\",\"authors\":\"A. Janssen, Wendy Jansen Holleboom, D. Rijkers, J. Louisse, Sjoerdtje A. Hoekstra, Sanne Schild, M. Vrolijk, Ron L. A. P. Hoogenboom, Karsten Beekmann\",\"doi\":\"10.3389/ftox.2024.1347965\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Exposure to PFASs is associated to several adverse health effects, such as immunotoxicity. Immunotoxic effects of PFOA and PFOS, including a reduced antibody response in both experimental animals and humans, have been reported. However, there is limited understanding of the underlying mechanisms involved. Moreover, there is only a restricted amount of immunotoxicity data available for a limited number of PFASs. In the current study the effects of 15 PFASs, including short- and long-chain perfluorinated carboxylic and sulfonic acids, fluorotelomer alcohols, and perfluoralkyl ether carboxylic acids were studied on the expression of recombinant activating gene 1 (RAG1) and RAG2 in the Namalwa human B lymphoma cell line, and on the human IL-2 promotor activity in Jurkat T-cells. Concentration-response data were subsequently used to derive in vitro relative potencies through benchmark dose analysis. In vitro relative potency factors (RPFs) were obtained for 6 and 9 PFASs based on their effect on RAG1 and RAG2 gene expression in Namalwa B-cells, respectively, and for 10 PFASs based on their inhibitory effect on IL-2 promotor activity in Jurkat T-cells. The most potent substances were HFPO-TA for the reduction of RAG1 and RAG2 gene expression in Namalwa cells (RPFs of 2.1 and 2.3 respectively), and PFDA on IL-2 promoter activity (RPF of 9.1). RAG1 and RAG2 play a crucial role in V (D)J gene recombination, a process for acquiring a varied array of antibodies crucial for antigen recognition. Hence, the effects observed in Namalwa cells might indicate a PFAS-induced impairment of generating a diverse range of B-cells essential for antigen recognition. The observed outcomes in the Jurkat T-cells suggest a possible PFAS-induced reduction of T-cell activation, which may contribute to a decline in the T-cell dependent antibody response. Altogether, the present study provides potential mechanistic insights into the reported PFAS-induced decreased antibody response. Additionally, the presented in vitro models may represent useful tools for assessing the immunotoxic potential of PFASs and prioritization for further risk assessment.\",\"PeriodicalId\":3,\"journal\":{\"name\":\"ACS Applied Electronic Materials\",\"volume\":\"7 5\",\"pages\":\"\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-03-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Electronic Materials\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3389/ftox.2024.1347965\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, ELECTRICAL & ELECTRONIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/ftox.2024.1347965","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
引用次数: 0
摘要
接触全氟辛烷磺酸会对健康产生多种不利影响,如免疫毒性。据报道,全氟辛烷磺酸和全氟辛烷磺酸具有免疫毒性效应,包括降低实验动物和人类的抗体反应。然而,人们对其中的基本机制了解有限。此外,目前只有有限的几种全氟辛烷磺酸的免疫毒性数据。本研究研究了 15 种 PFAS(包括短链和长链全氟羧酸和磺酸、氟甲苯醇和全氟烷基醚羧酸)对 Namalwa 人类 B 淋巴瘤细胞系中重组活化基因 1(RAG1)和 RAG2 的表达,以及对 Jurkat T 细胞中人类 IL-2 启动子活性的影响。浓度-反应数据随后被用于通过基准剂量分析得出体外相对效力。根据 6 种和 9 种全氟辛烷磺酸分别对 Namalwa B 细胞中 RAG1 和 RAG2 基因表达的影响,以及 10 种全氟辛烷磺酸对 Jurkat T 细胞中 IL-2 启动子活性的抑制作用,得出了这两种物质的体外相对效力因子 (RPF)。最有效的物质是 HFPO-TA(RPF 分别为 2.1 和 2.3)和 PFDA(RPF 为 9.1),前者可降低 Namalwa 细胞中 RAG1 和 RAG2 基因的表达。RAG1 和 RAG2 在 V (D)J 基因重组中起着关键作用,而 V (D)J 基因重组是获得对抗原识别至关重要的各种抗体的过程。因此,在纳玛尔瓦细胞中观察到的影响可能表明,PFAS 诱导的生成抗原识别所必需的各种 B 细胞的能力受损。在 Jurkat T 细胞中观察到的结果表明,PFAS 可能会诱导 T 细胞活化的减少,这可能会导致 T 细胞依赖性抗体反应的下降。总之,本研究为所报道的 PFAS 诱导的抗体反应下降提供了潜在的机理启示。此外,所介绍的体外模型可能是评估全氟辛烷磺酸免疫毒性潜力和确定进一步风险评估优先次序的有用工具。
Determination of in vitro immunotoxic potencies of a series of perfluoralkylsubstances (PFASs) in human Namalwa B lymphocyte and human Jurkat T lymphocyte cells
Exposure to PFASs is associated to several adverse health effects, such as immunotoxicity. Immunotoxic effects of PFOA and PFOS, including a reduced antibody response in both experimental animals and humans, have been reported. However, there is limited understanding of the underlying mechanisms involved. Moreover, there is only a restricted amount of immunotoxicity data available for a limited number of PFASs. In the current study the effects of 15 PFASs, including short- and long-chain perfluorinated carboxylic and sulfonic acids, fluorotelomer alcohols, and perfluoralkyl ether carboxylic acids were studied on the expression of recombinant activating gene 1 (RAG1) and RAG2 in the Namalwa human B lymphoma cell line, and on the human IL-2 promotor activity in Jurkat T-cells. Concentration-response data were subsequently used to derive in vitro relative potencies through benchmark dose analysis. In vitro relative potency factors (RPFs) were obtained for 6 and 9 PFASs based on their effect on RAG1 and RAG2 gene expression in Namalwa B-cells, respectively, and for 10 PFASs based on their inhibitory effect on IL-2 promotor activity in Jurkat T-cells. The most potent substances were HFPO-TA for the reduction of RAG1 and RAG2 gene expression in Namalwa cells (RPFs of 2.1 and 2.3 respectively), and PFDA on IL-2 promoter activity (RPF of 9.1). RAG1 and RAG2 play a crucial role in V (D)J gene recombination, a process for acquiring a varied array of antibodies crucial for antigen recognition. Hence, the effects observed in Namalwa cells might indicate a PFAS-induced impairment of generating a diverse range of B-cells essential for antigen recognition. The observed outcomes in the Jurkat T-cells suggest a possible PFAS-induced reduction of T-cell activation, which may contribute to a decline in the T-cell dependent antibody response. Altogether, the present study provides potential mechanistic insights into the reported PFAS-induced decreased antibody response. Additionally, the presented in vitro models may represent useful tools for assessing the immunotoxic potential of PFASs and prioritization for further risk assessment.
期刊介绍:
ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric.
Indexed/Abstracted:
Web of Science SCIE
Scopus
CAS
INSPEC
Portico