Impact on inflammation and recovery of skin barrier by nordihydroguaiaretic Acid as a protease-activated receptor 2 antagonist.

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-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 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.

• Authors: Hyo Young Kim, Jung Hyun Goo, Yeon Ah Joo, Ha Yoen Lee, Se Mi Lee, Chang Taek Oh, Soo Mi Ahn, Nam-Hoon Kim, Jae Sung Hwang
• Journal: Biomolecules & therapeutics (Biomol Ther (Seoul)) Vol. 20 Issue 5 Pg. 463-9 (Sep 2012) ISSN: 1976-9148 [Print] Korea (South)
• PMID: 24009835 (Publication Type: Journal Article)