Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway

Introduction: 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...

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Main Authors: Hye Ran Kim, So Yeon Lee, Ga Eun You, Chun Wook Park, Hye One Kim, Bo Young Chung
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Molecular Biosciences
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Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2023.1324692/full
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author Hye Ran Kim
So Yeon Lee
Ga Eun You
Chun Wook Park
Hye One Kim
Bo Young Chung
author_facet Hye Ran Kim
So Yeon Lee
Ga Eun You
Chun Wook Park
Hye One Kim
Bo Young Chung
author_sort Hye Ran Kim
collection DOAJ
description Introduction: 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).Methods: 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.Results and discussion: 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.
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spelling doaj-art-47a8a64348ea406e91a106387d3d6cd02025-08-20T02:09:08ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2024-01-011010.3389/fmolb.2023.13246921324692Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathwayHye Ran Kim0So Yeon Lee1Ga Eun You2Chun Wook Park3Hye One Kim4Bo Young Chung5Department of Dermatology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of KoreaDepartment of Dermatology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of KoreaResearch and Development Institute, Biosolution, Seoul, Republic of KoreaDepartment of Dermatology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of KoreaDepartment of Dermatology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of KoreaDepartment of Dermatology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of KoreaIntroduction: 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).Methods: 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.Results and discussion: 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.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1324692/fullexosomesbenzo[a]pyrenearyl hydrocarbon receptorpsoriasis2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
spellingShingle Hye Ran Kim
So Yeon Lee
Ga Eun You
Chun Wook Park
Hye One Kim
Bo Young Chung
Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway
Frontiers in Molecular Biosciences
exosomes
benzo[a]pyrene
aryl hydrocarbon receptor
psoriasis
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
title Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway
title_full Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway
title_fullStr Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway
title_full_unstemmed Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway
title_short Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway
title_sort exosomes released by environmental pollutant stimulated keratinocytes pbmcs can trigger psoriatic inflammation in recipient cells via the ahr signaling pathway
topic exosomes
benzo[a]pyrene
aryl hydrocarbon receptor
psoriasis
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
url https://www.frontiersin.org/articles/10.3389/fmolb.2023.1324692/full
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