Serine protease signaling of epidermal permeability barrier homeostasis

Jean Pierre Hachem, Evi Houben, Debra Crumrine, Mao Quiang Man, Nanna Schurer, Truus Roelandt, Eung Ho Choi, Yoshikazu Uchida, Barbara E. Brown, Kenneth R. Feingold, Peter M. Elias

Research output: Contribution to journalArticle

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Abstract

Evidence is growing that protease-activated receptor-2 (PAR-2) plays a key role in epithelial inflammation. We hypothesized here that PAR-2 plays a central role in epidermal permeability barrier homeostasis by mediating signaling from serine proteases (SP) in the stratum corneum (SC). Since the SC contains tryptic- and chymotryptic-like activity, we assessed the influence of SP activation/inhibition on barrier function. Acute barrier disruption increases SP activity and blockade by topical SP inhibitors (SPI) accelerates barrier recovery after acute abrogation. This improvement in barrier function is due to accelerated lamellar body (LB) secretion. Since tryptic SP signal certain downstream responses through PAR-2, we assessed its potential role in mediating the negative effects of SP on permeability barrier. Firstly, PAR-2 is expressed in the outer nucleated layers of the epidermis and most specifically under basal condition to the lipid raft (LR) domains. Secondly, tape stripping-induced barrier abrogation provokes PAR-2 activation, as shown by receptor internalization (i.e. receptor movement from LR to cytolpasmic domains). Thirdly, topical applications of PAR-2 agonist peptide, SLIGRL, delay permeability barrier recovery and inhibit LB secretion, while, conversely, PAR-2 knockout mice display accelerated barrier recovery kinetics and enhanced LB secretion, paralleled by increased LR formation and caveolin-1 expression. These results demonstrate first, the importance of SP/SPI balance for normal permeability barrier homeostasis, and second, they identify PAR-2 as a novel signaling mechanism of permeability barrier, that is, of response linked to LB secretion.

Original languageEnglish
Pages (from-to)2074-2086
Number of pages13
JournalJournal of Investigative Dermatology
Volume126
Issue number9
DOIs
Publication statusPublished - 2006 Sep 1

Fingerprint

PAR-2 Receptor
Serine Proteases
Permeability
Homeostasis
Serine Proteinase Inhibitors
seryl-leucyl-isoleucyl-glycyl-arginyl-leucine
Lipids
Recovery
Cornea
Chemical activation
Caveolin 1
Epidermis
Knockout Mice
Tapes
Inflammation
Peptides
Kinetics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Hachem, J. P., Houben, E., Crumrine, D., Man, M. Q., Schurer, N., Roelandt, T., ... Elias, P. M. (2006). Serine protease signaling of epidermal permeability barrier homeostasis. Journal of Investigative Dermatology, 126(9), 2074-2086. https://doi.org/10.1038/sj.jid.5700351
Hachem, Jean Pierre ; Houben, Evi ; Crumrine, Debra ; Man, Mao Quiang ; Schurer, Nanna ; Roelandt, Truus ; Choi, Eung Ho ; Uchida, Yoshikazu ; Brown, Barbara E. ; Feingold, Kenneth R. ; Elias, Peter M. / Serine protease signaling of epidermal permeability barrier homeostasis. In: Journal of Investigative Dermatology. 2006 ; Vol. 126, No. 9. pp. 2074-2086.
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Hachem, JP, Houben, E, Crumrine, D, Man, MQ, Schurer, N, Roelandt, T, Choi, EH, Uchida, Y, Brown, BE, Feingold, KR & Elias, PM 2006, 'Serine protease signaling of epidermal permeability barrier homeostasis', Journal of Investigative Dermatology, vol. 126, no. 9, pp. 2074-2086. https://doi.org/10.1038/sj.jid.5700351

Serine protease signaling of epidermal permeability barrier homeostasis. / Hachem, Jean Pierre; Houben, Evi; Crumrine, Debra; Man, Mao Quiang; Schurer, Nanna; Roelandt, Truus; Choi, Eung Ho; Uchida, Yoshikazu; Brown, Barbara E.; Feingold, Kenneth R.; Elias, Peter M.

In: Journal of Investigative Dermatology, Vol. 126, No. 9, 01.09.2006, p. 2074-2086.

Research output: Contribution to journalArticle

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AU - Hachem, Jean Pierre

AU - Houben, Evi

AU - Crumrine, Debra

AU - Man, Mao Quiang

AU - Schurer, Nanna

AU - Roelandt, Truus

AU - Choi, Eung Ho

AU - Uchida, Yoshikazu

AU - Brown, Barbara E.

AU - Feingold, Kenneth R.

AU - Elias, Peter M.

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Hachem JP, Houben E, Crumrine D, Man MQ, Schurer N, Roelandt T et al. Serine protease signaling of epidermal permeability barrier homeostasis. Journal of Investigative Dermatology. 2006 Sep 1;126(9):2074-2086. https://doi.org/10.1038/sj.jid.5700351