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

• Published in: Biomolecules & therapeutics Vol. 20; no. 5; pp. 463 - 469
• Main Authors: 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
• Format: Journal Article
• Language: Korean
• Published: 한국응용약물학회 30.09.2012
• Subjects: Atopic dermatitis; Nordihydroguaiaretic acid; PAR2 antagonist; Protease activated receptor 2; Skin barrier; PAR2 antagonist; Skin barrier; Atopic dermatitis; Nordihydroguaiaretic acid; Protease activated receptor 2
• ISSN: 1976-9148; 2005-4483

serAtopic 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.