gamma-Tocotrienol reduces squalene hydroperoxide-induced inflammatory responses in HaCaT keratinocytes.
Squalene hydroperoxide (SQ-OOH), the primary peroxidation product of squalene (SQ), accumulates at the surface of sunlight-exposed human skin. There are however only a few studies on the pathogenic actions (i.e., inflammatory stimuli) of SQ-OOH. Here, we evaluated whether SQ-OOH induced inflammatory responses in immortalized human keratinocytes (HaCaT). We found that SQ-OOH caused an increase in the expression of inflammatory genes such as the interleukins as well as cyclooxygenase-2 (COX-2). In concordance with the upregulation of COX-2 mRNA, SQ-OOH enhanced reactive oxygen species generation, nuclear factor kappa B activation, COX-2 protein expression, and prostaglandin E2 production. Therefore, the pro-inflammatory effects of SQ-OOH may be mediated in part via COX-2. On the other hand, gamma-tocotrienol (gamma-T3, an unsaturated form of vitamin E) was found to ameliorate the SQ-OOH actions. These results suggest that SQ-OOH induces inflammatory responses in HaCaT, implying that SQ-OOH plays an important role in inflammatory skin disorders. As a preventive strategy, inflammation could be reduced via the use of gamma-T3.
Nakagawa
Kiyotaka
K
Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan. nkgw@biochem.tohoku.ac.jp
Shibata
Akira
A
Maruko
Toru
T
Sookwong
Phumon
P
Tsuduki
Tsuyoshi
T
Kawakami
Kayoko
K
Nishida
Hiroshi
H
Miyazawa
Teruo
T
D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013185:Squalene / Q000031:analogs & derivatives* / Q000633:toxicity; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
C002821:2,3-oxidosqualene; D002839:Chromans; D018836:Inflammation Mediators; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014810:Vitamin E; C013649:plastochromanol 8; D013185:Squalene; D051546:Cyclooxygenase 2