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http://dx.doi.org/10.4062/biomolther.2012.20.5.463

Impact on Inflammation and Recovery of Skin Barrier by Nordihydroguaiaretic Acid as a Protease-Activated Receptor 2 Antagonist  

Kim, Hyo-Young (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University)
Goo, Jung-Hyun (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University)
Joo, Yeon-Ah (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University)
Lee, Ha-Yoen (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University)
Lee, Se-Mi (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University)
Oh, Chang-Taek (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University)
Ahn, Soo-Mi (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University)
Kim, Nam-Hoon (Sehwa High School)
Hwang, Jae-Sung (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University)
Publication Information
Biomolecules & Therapeutics / v.20, no.5, 2012 , pp. 463-469 More about this Journal
Abstract
Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.
Keywords
Protease activated receptor 2; Atopic dermatitis; Skin barrier; Nordihydroguaiaretic acid; PAR2 antagonist;
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