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
{"title":"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","authors":"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","doi":"10.1002/jat.4623","DOIUrl":null,"url":null,"abstract":"<p>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. <i>CYP1A1</i>, <i>CYP1A2</i>, <i>CYP1B1</i>, <i>CYP2A6</i>, and <i>CYP2A13</i> 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 <i>CYP1A2</i> and <i>CYP1B1</i> 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 <i>CYP1B1</i> was found in mDC-CA-exposed and between IL-12p70 and <i>CYP1A1</i> was found in BEAS-2B after CA exposure. However, IL-12p70 and <i>CYP1A2</i> as well as IL-18, IL-33, and <i>CYP1A1</i> 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.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 9","pages":"1317-1328"},"PeriodicalIF":2.7000,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exposure of cinnamyl alcohol in co-culture of BEAS-2B and dendritic cells: Interaction between CYP450 and cytokines\",\"authors\":\"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\",\"doi\":\"10.1002/jat.4623\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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. <i>CYP1A1</i>, <i>CYP1A2</i>, <i>CYP1B1</i>, <i>CYP2A6</i>, and <i>CYP2A13</i> 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 <i>CYP1A2</i> and <i>CYP1B1</i> 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 <i>CYP1B1</i> was found in mDC-CA-exposed and between IL-12p70 and <i>CYP1A1</i> was found in BEAS-2B after CA exposure. 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Exposure of cinnamyl alcohol in co-culture of BEAS-2B and dendritic cells: Interaction between CYP450 and cytokines
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.
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.