1. ¹Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
2. ²Neopharm, Daejeon, Korea
3. ³Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea
4. ⁴Department of Dermatology, Wonju College of Medicine, Yonsei University, Wonju, Korea
5. ⁵Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
6. ⁶Department of Oral Biochemistry, Oral Science Research Center, Brain Korea 21 Project, Yonsei University College of Dentistry, Seoul, Korea

Correspondence: Dr Seung Hun Lee, Department of Dermatology, Yongdong Severance Hospital, Yonsei University College of Medicine, no. 146-92, Dogok-dong, Kangnam-gu, Seoul 135-720, Korea. E-mail: ydshderm@yumc.yonsei.ac.kr

Received 5 September 2006; Revised 29 November 2007; Accepted 14 December 2007; Published online 28 February 2008.

Abstract

Protease-activated receptor-2 (PAR-2) is known to be involved in epidermal permeability barrier function homeostasis. PAR-2 activation occurs after barrier disruption and further activation of PAR-2 by activating peptide significantly delays barrier recovery rate. Cockroach and house dust mite allergens, both known to be associated with the development of asthma, allergic rhinitis, and atopic dermatitis, have protease activity, which can activate PAR-2. In this study, we investigated the effects of both allergens on the epidermal barrier function as well as on the epidermal calcium gradient. Both allergens, when topically applied on the barrier-disrupted site, increased protease activities in the epidermis and delayed barrier recovery and lamellar body secretion in murine skin. The topical application of PAR-2-specific antagonist or protease inhibitors normalized the barrier recovery. Cockroach allergens induced intracellular calcium oscillations in cultured human keratinocytes through PAR-2-involved pathway, which was confirmed by desensitization protocol. Abnormal calcium ion distribution after barrier disruption was also observed in allergens-applied skin. These results suggest that allergens with protease activity can influence the epidermal permeability barrier homeostasis through PAR-2 activation and consequent modulation of the calcium ions in skin.