Impact of Nrf2 on UVB-induced skin inflammation/photoprotection and photoprotective effect of sulforaphane

Mol Carcinog. 2011 Jun;50(6):479-86. doi: 10.1002/mc.20725. Epub 2010 Dec 28.

Abstract

Ultraviolet (UV) of sunlight is a complete carcinogen that can burn skin, enhance inflammation, and drive skin carcinogenesis. Previously, we have shown that sulforaphane (SFN) inhibited chemically induced skin carcinogenesis via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and others have shown that broccoli sprout extracts containing high SFN protected against UV-induced skin carcinogenesis in SKH-1 hairless mice. A recent study showed that there was no difference between Nrf2 knockout (Nrf2 KO) and Nrf2 wild-type (WT) BALB/C mice after exposing to high dose of UVB. Since Nrf2 plays critical roles in the anti-oxidative stress/anti-inflammatory responses, it is relevant to assess the role of Nrf2 for photoprotection against UV. In this context, the role of Nrf2 in UVB-induced skin inflammation in Nrf2 WT and Nrf2 KO C57BL/6 mice was studied. A single dose of UVB (300 mJ/cm(2)) resulted in skin inflammation in both WT and Nrf2 KO (-/-) mice (KO mice) at 8 h and 8 d following UVB irradiation. In the WT mice inflammation returned to the basal level to a greater extent when compared to the KO mice. SFN treatment of Nrf2 WT but not Nrf2 KO mice restored the number of sunburn cells back to their basal level by 8 d after UVB irradiation. Additionally, UVB-induced short-term inflammatory biomarkers (interleukin-1β and interleukin-6) were increased in the KO mice and UVB-induced apoptotic cells in the KO mice were significantly higher as compared to that in the WT. Taken together, our results show that functional Nrf2 confers a protective effect against UVB-induced inflammation, sunburn reaction, and SFN-mediated photoprotective effects in the skin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / therapeutic use*
  • Dermatitis / drug therapy*
  • Dermatitis / etiology
  • Dermatitis / pathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunoenzyme Techniques
  • Isothiocyanates
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-E2-Related Factor 2 / physiology*
  • Radiation-Protective Agents / therapeutic use
  • Sunburn / drug therapy
  • Sunburn / etiology
  • Sunburn / pathology
  • Thiocyanates / therapeutic use*
  • Ultraviolet Rays / adverse effects*

Substances

  • Anticarcinogenic Agents
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Radiation-Protective Agents
  • Thiocyanates
  • sulforafan