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.