Falconer-Turner April, Brooks Kameron, Ogaga Eseoghene, Whalen Margaret M
Department of Biological Sciences, Tennessee State University, Nashville, TN, USA.
Department of Chemistry, Tennessee State University, Nashville, TN, USA.
J Appl Toxicol. 2025 Feb;45(2):273-287. doi: 10.1002/jat.4700. Epub 2024 Sep 17.
Hexabromocyclododecane (HBCD) is an environmental contaminant due to its use as a flame retardant in a variety of applications ranging from building insulation, furniture upholstery, and housing for appliances and electronics. HBCD is found in wildlife, human breastmilk, and serum. Interleukin 1-beta (IL-1β) and interleukin 6 (IL-6) are pro-inflammatory cytokines, whose dysregulation is associated with chronic inflammation and the pathologies that result, such as tumor growth, rheumatoid arthritis, Crohn's disease, and multiple sclerosis. HBCD has been shown to increase the secretion of both IL-1β and IL-6 from human immune cells. However, it is not clear if these increases are due solely to HBCD effects on the secretory process or whether it is stimulating cellular production of IL-1β and IL-6. This study examines if HBCD can increase the production of IL-1β and IL-6 by immune cells by simultaneously assessing secreted levels and cellular levels of these cytokines. Additionally, the mechanisms for any observed changes in production are investigated. Peripheral blood mononuclear cells were exposed to HBCD over a range of concentrations and lengths of exposure. HBCD was found to stimulate IL-1β and IL-6 production after 6 hrs. of exposure and production was sustained and intensified at 24 hrs. This increase in IL-1β and IL-6 production appears to, in part, be a result of increased mRNA expression. Additionally, the MAPK pathways, specifically the p38 and p44/42 pathways, appear to be required for HBCD-induced increases in IL-1β and IL-6 production.
六溴环十二烷（HBCD）是一种环境污染物，因为它在多种应用中用作阻燃剂，包括建筑隔热材料、家具内饰以及电器和电子产品外壳。在野生动物、人类母乳和血清中都能发现HBCD。白细胞介素1-β（IL-1β）和白细胞介素6（IL-6）是促炎细胞因子，其失调与慢性炎症以及由此导致的病理状况相关，如肿瘤生长、类风湿性关节炎、克罗恩病和多发性硬化症。已证明HBCD会增加人类免疫细胞中IL-1β和IL-6的分泌。然而，尚不清楚这些增加是否仅归因于HBCD对分泌过程的影响，还是它刺激了IL-1β和IL-6的细胞产生。本研究通过同时评估这些细胞因子的分泌水平和细胞水平，来检测HBCD是否能增加免疫细胞产生IL-1β和IL-6。此外，还研究了所观察到的产生变化的机制。将外周血单核细胞暴露于一系列浓度和暴露时长的HBCD中。发现暴露6小时后HBCD会刺激IL-1β和IL-6的产生，并且在24小时时产生持续且增强。IL-1β和IL-6产生的这种增加似乎部分是mRNA表达增加的结果。此外，丝裂原活化蛋白激酶（MAPK）途径，特别是p38和p44/42途径，似乎是HBCD诱导IL-1β和IL-6产生增加所必需的。
