| Autor: |
Yea Seong Ryu, Kyoung Ah Kang, Mei Jing Piao, Mee Jung Ahn, Joo Mi Yi, Young-Min Hyun, Seo Hyeong Kim, Min Kyung Ko, Chang Ook Park, Jin Won Hyun |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Redox Biology, Vol 21, Iss , Pp - (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2018.101080 |
| Popis: |
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 through MyD88, and led to the translocation of NFκB to the nucleus, where it bound the NFκB site within IL-6 promoter. Furthermore, PM2.5 induced a direct interaction between TLR5 and NOX4, and in turn induced the production of ROS and activated NFκB-IL-6 downstream, which was prevented by siRNA-mediated knockdown of NOX4 or antioxidant treatment. Furthermore, expression of TLR5, MyD88, NOX4, phospho-NFκB, and IL-6 was increased in skin tissue of PM2.5-treated flaky tail mice. PM2.5-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 PM2.5 exposure and can be used as a therapeutic strategy to treat inflammatory skin diseases caused by PM2.5 exposure. Keywords: Particulate matter, Interleukin-6, Reactive oxygen species, Toll like receptor, Epigenetic modification |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
