Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery.
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.
Jeong
Se Kyoo
SK
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Kim
Hyun Jeong
HJ
Youm
Jong-Kyung
JK
Ahn
Sung Ku
SK
Choi
Eung Ho
EH
Sohn
Myung Hyun
MH
Kim
Kyu-Earn
KE
Hong
Jeong Hee
JH
Shin
Dong Min
DM
Lee
Seung Hun
SH
D000328:Adult; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001706:Biopsy; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D003058:Cockroaches; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006706:Homeostasis / Q000276:immunology / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology
D039741:Antigens, Dermatophagoides; D044464:Receptor, PAR-2; D002118:Calcium