Exposure of cinnamyl alcohol in co-culture of BEAS-2B and dendritic cells: Interaction between CYP450 and cytokines

IF 2.7 4区 医学 Q3 TOXICOLOGY
Kelly Yoshizaki, Daniela Perroni Frias, Kevin Maier, Juliana Smelan, Aristides Tadeu Correia, Luanda Mara da Silva Oliveira, Luís Fernando Amato-Lourenço, Bruna Tereso Santillo, Carla Máximo Prado, Telma Miyuki Oshiro, Jose Alexandre M. Barbuto, Thais Mauad, Mariangela Macchione
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引用次数: 0

Abstract

The prevalence of fragrances in various hygiene products contributes to their sensorial allure. However, fragrances can induce sensitization in the skin or respiratory system, and the mechanisms involved in this process are incompletely understood. This study investigated the intricate mechanisms underlying the fragrance's effects on sensitization response, focusing on the interplay between CYP450 enzymes, a class of drug-metabolizing enzymes, and the adaptive immune system. Specifically, we assessed the expression of CYP450 enzymes and cytokine profiles in culture of BEAS-2B and mature dendritic cells (mDC) alone or in co-culture stimulated with 2 mM of a common fragrance, cinnamyl alcohol (CA) for 20 h. CYP1A1, CYP1A2, CYP1B1, CYP2A6, and CYP2A13 were analyzed by RT-PCR and IL-10, IL-12p70, IL-18, IL-33, and thymic stromal lymphopoietin (TSLP) by Cytometric Bead Array (CBA). Through RT–PCR analysis, we observed that CA increased CYP1A2 and CYP1B1 expression in BEAS-2B, with a further increased in BEAS-2B-mDC co-culture. Additionally, exposure to CA increased IL-12p70 levels in mDC rather than in BEAS-2B-mDC co-culture. In regards to IL-18, level was higher in BEAS-2B than in BEAS-2B-mDC co-culture. A positive correlation between the levels of IL-10 and CYP1B1 was found in mDC-CA-exposed and between IL-12p70 and CYP1A1 was found in BEAS-2B after CA exposure. However, IL-12p70 and CYP1A2 as well as IL-18, IL-33, and CYP1A1 levels were negative, correlated mainly in co-culture control. These correlations highlight potential immunomodulatory interactions and complex regulatory relationships. Overall, exposure to CA enhances CYP450 expression, suggesting that CA can influence immune responses by degrading ligands on xenosensitive transcription factors.

肉桂醇在 BEAS-2B 和树突状细胞共培养中的暴露:CYP450与细胞因子之间的相互作用
各种卫生用品中普遍使用香料,这也是其感官诱惑的原因之一。然而,香料会诱发皮肤或呼吸系统的过敏反应,而人们对这一过程的相关机制还不甚了解。本研究以 CYP450 酶(一类药物代谢酶)和适应性免疫系统之间的相互作用为重点,研究了香料影响致敏反应的复杂机制。具体来说,我们评估了在 2 mM 常见香料肉桂醇(CA)刺激下单独或共培养 20 小时的 BEAS-2B 和成熟树突状细胞(mDC)中 CYP450 酶的表达和细胞因子谱。通过 RT-PCR 分析了 CYP1A1、CYP1A2、CYP1B1、CYP2A6 和 CYP2A13,通过细胞计数珠阵列(CBA)分析了 IL-10、IL-12p70、IL-18、IL-33 和胸腺基质淋巴细胞生成素(TSLP)。通过 RT-PCR 分析,我们观察到 CA 增加了 BEAS-2B 中 CYP1A2 和 CYP1B1 的表达,并在 BEAS-2B-mDC 共培养中进一步增加。此外,暴露于CA会增加mDC中的IL-12p70水平,而不是BEAS-2B-mDC共培养中的IL-12p70水平。IL-18在BEAS-2B中的水平高于在BEAS-2B-mDC共培养中的水平。在暴露于 CA 的 mDC 中,IL-10 和 CYP1B1 的水平呈正相关;在暴露于 CA 的 BEAS-2B 中,IL-12p70 和 CYP1A1 的水平呈正相关。然而,IL-12p70 和 CYP1A2 以及 IL-18、IL-33 和 CYP1A1 水平呈负相关,主要是在共培养对照中。这些相关性凸显了潜在的免疫调节相互作用和复杂的调节关系。总之,暴露于CA会增强CYP450的表达,这表明CA可以通过降解异种敏感转录因子上的配体来影响免疫反应。
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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
期刊介绍: Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.
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