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KMID : 0606920120200050463
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Biomolecules & Therapeutics
2012 Volume.20 No. 5 p.463 ~ p.469
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Impact on Inflammation and Recovery of Skin Barrier by Nordihydroguaiaretic Acid as a Protease-Activated Receptor 2 Antagonist
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Kim Hyo-Young
Goo Jung-Hyun
Joo Yeon-Ah
Lee Ha-Yoen
Lee Se-Mi
Oh Chang-Taek
Ahn Soo-Mi
Kim Nam-Hoon
Hwang Jae-Sung
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Abstract
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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-NH2. 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 Ca2+ 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.
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KEYWORD
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Protease activated receptor 2, Atopic dermatitis, Skin barrier, Nordihydroguaiaretic acid, PAR2 antagonist
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