Kim Hye Ran, Lee So Yeon, You Ga Eun, Park Chun Wook, Kim Hye One, Chung Bo Young
Department of Dermatology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.
Research and Development Institute, Biosolution, Seoul, Republic of Korea.
Front Mol Biosci. 2024 Jan 15;10:1324692. doi: 10.3389/fmolb.2023.1324692. eCollection 2023.
Exosomes, pivotal in intercellular communication during skin disease pathogenesis, have garnered substantial attention. However, the impact of environmental pollutants, such as benzo[a]pyrene (BaP) and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), on exosome release amid inflammatory skin diseases remains unexplored. This study addresses this gap by examining the influence of BaP and TCDD on exosome function, specifically focusing on immune-related pathway alterations in normal recipient keratinocytes and peripheral blood mononuclear cells (PBMCs). HaCaT cells were treated with exosomes from BaP- or TCDD-treated keratinocytes. Proinflammatory cytokines and chemokines, including TNF-α, IL-1β, IL-6, IL-8, CXCL1, and CXCL5, were assessed. The involvement of the p65NF-κB/p38MAPK/ERK signaling pathway in recipient keratinocytes was investigated. Aryl hydrocarbon receptor (AhR) silencing was employed to elucidate its role in mediating the proinflammatory response induced by exosomes from BaP- or TCDD-treated keratinocytes. Treatment with exosomes from BaP- or TCDD-treated keratinocytes induced a significant increase in proinflammatory cytokines and chemokines in HaCaT cells. The upregulation implicated the p65NF-κB/p38MAPK/ERK signaling pathway. AhR silencing attenuated this response, suggesting a role for AhR in mediating this response. In PBMCs from healthy controls, exosomes from BaP-stimulated PBMCs of psoriatic patients led to increased expression of proinflammatory cytokines and modulation of Th1/Th17 cell distribution via AhR activation. These findings unveil a novel dimension in the interplay between environmental xenobiotic agents (BaP and TCDD) and exosomal functions. The study establishes their influence on psoriatic inflammatory responses, shedding light on the underlying mechanisms mediated through the AhR signaling pathway in recipient keratinocytes and PBMCs.
外泌体在皮肤病发病机制的细胞间通讯中起关键作用，已受到广泛关注。然而，环境污染物如苯并[a]芘（BaP）和2,3,7,8-四氯二苯并对二恶英（TCDD）在炎症性皮肤病中对外泌体释放的影响仍未得到探索。本研究通过检测BaP和TCDD对外泌体功能的影响来填补这一空白，特别关注正常受体角质形成细胞和外周血单核细胞（PBMC）中免疫相关途径的改变。用来自BaP或TCDD处理的角质形成细胞的外泌体处理HaCaT细胞。评估促炎细胞因子和趋化因子，包括TNF-α、IL-1β、IL-6、IL-8、CXCL1和CXCL5。研究了受体角质形成细胞中p65NF-κB/p38MAPK/ERK信号通路的参与情况。采用芳烃受体（AhR）沉默来阐明其在介导BaP或TCDD处理的角质形成细胞的外泌体诱导的促炎反应中的作用。用来自BaP或TCDD处理的角质形成细胞的外泌体处理可导致HaCaT细胞中促炎细胞因子和趋化因子显著增加。上调涉及p65NF-κB/p38MAPK/ERK信号通路。AhR沉默减弱了这种反应，表明AhR在介导这种反应中起作用。在健康对照的PBMC中，来自银屑病患者BaP刺激的PBMC的外泌体通过AhR激活导致促炎细胞因子表达增加和Th1/Th17细胞分布的调节。这些发现揭示了环境异源生物制剂（BaP和TCDD）与外泌体功能之间相互作用的新层面。该研究确定了它们对银屑病炎症反应的影响，揭示了通过受体角质形成细胞和PBMC中的AhR信号通路介导的潜在机制。
