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Archives of Pharmacal Research

, Volume 40, Issue 9, pp 1105–1116 | Cite as

Pro-oxidant status and Nrf2 levels in psoriasis vulgaris skin tissues and dimethyl fumarate-treated HaCaT cells

  • Yoon Jin Lee
  • Jin Ho Bae
  • Sang-Gue Kang
  • Sung Woo Cho
  • Dong-Il Chun
  • Seung Min Nam
  • Chul Han Kim
  • Hae Seon Nam
  • Seon Hwa Lee
  • Sang Han Lee
  • Moon Kyun ChoEmail author
Research Article

Abstract

Reactive oxygen species (ROS) contribute to pathogenesis of many inflammatory skin diseases, including psoriasis. The aim of this study is to compare antioxidant protein expression in psoriasis vulgaris (PV) skin tissues with that in normal skin tissues in vivo and to evaluate the effects of dimethyl fumarate (DMF), used for the treatment of psoriasis, on ROS generation and apoptosis in a human keratinocyte cell line HaCaT. Compared with normal skin tissues, PV skin tissues showed increased protein oxidation as well as down-regulation of Nrf2 and its regulatory proteins such as HO-1 and AKR1C3. Using HaCaT cells to model DMF-induced pro-oxidant effects in the skin cells, we found that DMF treatment induced increased ROS levels and apoptotic cell death, as signified by increased proportion of cells with Annexin V-PE(+) staining and a sub-G0/G1 peak in the cell cycle. Preceding these changes, DMF treatment resulted in up-regulation of Nrf2, HO-1, and AKR1C3 proteins in these cells. Collectively, increased oxidative stress and impaired cellular anti-oxidant enzyme systems may participate in the pathogenesis of PV. DMF may exert an additive therapeutic efficacy in PV by attenuating the redox burden and subsequent oxidative damage to normal keratinocytes through activation of Nrf2 pathway relative to PV.

Keywords

Antioxidant protein Nrf2 Psoriasis DMF 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that there are no competing interests in this manuscript.

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Copyright information

© The Pharmaceutical Society of Korea 2017

Authors and Affiliations

  • Yoon Jin Lee
    • 1
  • Jin Ho Bae
    • 2
  • Sang-Gue Kang
    • 1
  • Sung Woo Cho
    • 1
  • Dong-Il Chun
    • 1
  • Seung Min Nam
    • 1
  • Chul Han Kim
    • 1
  • Hae Seon Nam
    • 1
  • Seon Hwa Lee
    • 1
  • Sang Han Lee
    • 1
  • Moon Kyun Cho
    • 2
    Email author
  1. 1.Molecular Cancer ResearchSoonchunhyang University College of MedicineCheonan-siRepublic of Korea
  2. 2.Department of DermatologySoonchunhyang University HospitalSeoulRepublic of Korea

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