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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

 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 
 Redox Biology, Vol.21 : 101080, 2019 
Journal Title
 Redox Biology 
Issue Date
Epigenetic modification ; Interleukin-6 ; Particulate matter ; Reactive oxygen species ; Toll like receptor
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.
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Park, Chang Ook(박창욱) ORCID logo https://orcid.org/0000-0003-3856-1201
Hyun, Young-Min(현영민) ORCID logo https://orcid.org/0000-0002-0567-2039
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