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γ-Tocotrienol Reduces Squalene Hydroperoxide-Induced Inflammatory Responses in HaCaT Keratinocytes

  • Original Article
  • Published:
Lipids

Abstract

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, γ-tocotrienol (γ-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 γ-T3.

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Abbreviations

COX-2:

Cyclooxygenase-2

DCDHF:

2,7-Dichlorodihydrofluorescein

DMEM:

Dulbecco’s modified Eagle medium

FBS:

Fetal bovine serum

HaCaT:

Human keratinocytes

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

NF-κB:

Nuclear factor kappa B

PGE2:

Prostaglandin E2

SQ:

Squalene

SQ-OOH:

Squalene hydroperoxide

ROS:

Reactive oxygen species

T3:

Tocotrienol

TNF-α:

Tumor necrosis factor-α

UV:

Ultraviolet

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Acknowledgments

We thank Prof. Norimichi Nakahata (Graduate School of Pharmaceutical Sciences, Tohoku University, Japan) for the donation of HaCaT, and Dr. Tadashi Uchino (National Institute of Health Sciences, Tokyo, Japan) for excellent technical advice. A part of this study was supported by KAKENHI (20228002 and 22780110) of JSPS, Japan. Financial support was also provided by the Foundation of Oil and Fat Industry Kaikan, Japan.

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Authors and Affiliations

  1. Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan

    Kiyotaka Nakagawa, Akira Shibata, Toru Maruko, Phumon Sookwong & Teruo Miyazawa

  2. Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan

    Tsuyoshi Tsuduki

  3. Niigata University of Pharmacy and Applied Life Sciences, Niigata, 956-8603, Japan

    Kayoko Kawakami & Hiroshi Nishida

Authors
  1. Kiyotaka Nakagawa
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  2. Akira Shibata
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Correspondence to Kiyotaka Nakagawa.

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Nakagawa, K., Shibata, A., Maruko, T. et al. γ-Tocotrienol Reduces Squalene Hydroperoxide-Induced Inflammatory Responses in HaCaT Keratinocytes. Lipids 45, 833–841 (2010). https://doi.org/10.1007/s11745-010-3458-4

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  • DOI: https://doi.org/10.1007/s11745-010-3458-4

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