Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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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)
  • Received : 2012.06.11
  • Accepted : 2012.07.17
  • Published : 2012.09.30
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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

References

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