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.
Bibliographical noteFunding Information:
This work was supported by Grant No. R-01-2006-000-10997-0 from the Basic Research Program of the Korea Science and Engineering Foundation. We are grateful to Tai-Soon Yong, MD, and Kyoung Yong Jeong, PhD, for the generous gifts of the dust mite allergens and cockroach allergens, and also grateful to Han Young Kim, PhD, for synthesizing PAR-2-specific antagonist, ENMD-1,068.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology