title: Impact of Nrf2 on UVB-induced skin inflammation/photoprotection and photoprotective effect of sulforaphane.
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.
authors.affiliation: Center for Cancer Prevention Research, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Constance L
authors.initials: CL
authors.lastname: Saw
authors.forename: Mou-Tuan
authors.initials: MT
authors.lastname: Huang
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Tin Oo
authors.initials: TO
authors.lastname: Khor
authors.forename: Allan H
authors.initials: AH
authors.lastname: Conney
authors.forename: Ah-Ng
authors.initials: AN
authors.lastname: Kong
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D003872:Dermatitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007124:Immunoenzyme Techniques; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D013454:Sulfoxides; D013471:Sunburn / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D013861:Thiocyanates / Q000627:therapeutic use*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D011837:Radiation-Protective Agents; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane