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Particulate matter induces inflammatory cytokine production via activation of NF?B by TLR5-NOX4-ROS signaling in human skin keratinocyte and mouse skin.

ABSTRACT: Particulate matter (PM) increases levels of pro-inflammatory cytokines, but its effects on the skin remain largely unknown. We investigated the signal transduction pathway and epigenetic regulatory mechanisms underlying cellular inflammation induced by PM with a diameter of ??2.5 (PM_2.5) in vitro and in vivo. PM_2.5-treated skin keratinocytes produced various inflammatory cytokines, including IL-6. The binding of PM_2.5 to TLR5 initiated intracellular signaling through MyD88, and led to the translocation of NF?B to the nucleus, where it bound the NF?B site within IL-6 promoter. Furthermore, PM_2.5 induced a direct interaction between TLR5 and NOX4, and in turn induced the production of ROS and activated NF?B-IL-6 downstream, which was prevented by siRNA-mediated knockdown of NOX4 or antioxidant treatment. Furthermore, expression of TLR5, MyD88, NOX4, phospho-NF?B, and IL-6 was increased in skin tissue of PM_2.5-treated flaky tail mice. PM_2.5-induced increased transcription of IL-6 was regulated via DNA methylation and histone methylation by epigenetic modification; the binding of DNA demethylase and histone methyltransferase to the IL-6 promoter regions resulted in increased IL-6 mRNA expression. Our findings provide deep insight into the pathogenesis of PM_2.5 exposure and can be used as a therapeutic strategy to treat inflammatory skin diseases caused by PM_2.5 exposure.

SUBMITTER: Ryu YS

PROVIDER: S-EPMC6305701 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Particulate matter induces inflammatory cytokine production via activation of NFκB by TLR5-NOX4-ROS signaling in human skin keratinocyte and mouse skin.

Ryu Yea Seong YS Kang Kyoung Ah KA Piao Mei Jing MJ Ahn Mee Jung MJ Yi Joo Mi JM Hyun Young-Min YM Kim Seo Hyeong SH Ko Min Kyung MK Park Chang Ook CO Hyun Jin Won JW

Redox biology 20181215

Particulate matter (PM) increases levels of pro-inflammatory cytokines, but its effects on the skin remain largely unknown. We investigated the signal transduction pathway and epigenetic regulatory mechanisms underlying cellular inflammation induced by PM with a diameter of ≤ 2.5 (PM2.5) in vitro and in vivo. PM2.5-treated skin keratinocytes produced various inflammatory cytokines, including IL-6. The binding of PM2.5 to TLR5 initiated intracellular signaling thr ...[more]

PMID: 30584981

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Project description:The human skin is exposed to various environmental factors including solar radiation and ambient air pollutants. Although, due to its physical and biological properties, the skin efficiently protects the body against the harm of environmental factors, their excessive levels and possible synergistic action may lead to harmful effects. Among particulate matter present in ambient air pollutants, PM2.5 is of particular importance for it can penetrate both disrupted and intact skin, causing adverse effects to skin tissue. Although certain components of PM2.5 can exhibit photochemical activity, only a limited amount of data regarding the interaction of PM2.5 with light and its effect on skin tissue are available. This study focused on light-induced toxicity in cultured human keratinocytes, which was mediated by PM2.5 obtained in different seasons. Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM) were employed to determine sizes of the particles. The ability of PM2.5 to photogenerate free radicals and singlet oxygen was studied using EPR spin-trapping and time-resolved singlet oxygen phosphorescence, respectively. Solar simulator with selected filters was used as light source for cell treatment to model environmental lightning conditions. Cytotoxicity of photoexcited PM2.5 was analyzed using MTT assay, PI staining and flow cytometry, and the apoptotic pathway was further examined using Caspase-3/7 assay and RT-PCR. Iodometric assay and JC-10 assay were used to investigate damage to cell lipids and mitochondria. Light-excited PM2.5 were found to generate free radicals and singlet oxygen in season-dependent manner. HaCaT cells containing PM2.5 and irradiated with UV-Vis exhibited oxidative stress features-increased peroxidation of intracellular lipids, decrease of mitochondrial membrane potential, enhanced expression of oxidative stress related genes and apoptotic cell death. The data indicate that sunlight can significantly increase PM2.5-mediated toxicity in skin cells.

Dataset Information

Particulate matter induces inflammatory cytokine production via activation of NF?B by TLR5-NOX4-ROS signaling in human skin keratinocyte and mouse skin.

Publications

Particulate matter induces inflammatory cytokine production via activation of NFκB by TLR5-NOX4-ROS signaling in human skin keratinocyte and mouse skin.

Similar Datasets

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