The skin barrier is the body's defense against infections and environmental insults. Antimicrobial peptides (AMPs) expressed in human skin, including defensins and cathelicidin, play an important role in host defense against pathogens by killing microbes, but may also affect inflammation, angiogenesis, and wound healing [
]. Aberg et al. reported that the epidermal permeability barrier was abnormal in CRAMP (murine homolog of human cathelicidin LL-37) knock out mice, suggesting that AMPs may affect epidermal permeability [
- Nakatsuji T.
- Gallo R.L.
Antimicrobial peptides: old molecules with new ideas.
J Invest Dermatol. 2012; 132: 887-895
]. As tight junctions (TJs) are a key component of the permeability barrier [
- Aberg K.M.
- Man M.Q.
- Gallo R.L.
- Ganz T.
- Crumrine D.
- Brown B.E.
- et al.
Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers.
J Invest Dermatol. 2008; 128: 917-975
- Kirschner N.
- Houdek P.
- Fromm M.
- Moll I.
- Brandner J.M.
Tight junctions form a barrier in human epidermis.
Eur J Cell Biol. 2010; 89: 839-842
4], we hypothesized that AMPs regulate the permeability barrier by affecting TJs. Thus, we investigated whether human beta defensin-1 (hBD-1) – an AMP expressed ubiquitously in the epidermis that is known to affect keratinocyte function – regulates the development of TJs and the formation of the epidermal permeability barrier.
- Furuse M.
- Hata M.
- Furuse K.
- Yoshida Y.
- Haratake A.
- Sugitani Y.
- et al.
Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice.
J Cell Biol. 2002; 156: 1099-1111
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- Antimicrobial peptides: old molecules with new ideas.J Invest Dermatol. 2012; 132: 887-895
- Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers.J Invest Dermatol. 2008; 128: 917-975
- Tight junctions form a barrier in human epidermis.Eur J Cell Biol. 2010; 89: 839-842
- Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice.J Cell Biol. 2002; 156: 1099-1111
- Nonreceptor tyrosine kinase c-Yes interacts with occludin during tight junction formation in canine kidney epithelial cells.Mol Biol Cell. 2002; 13: 1227-1237
- Detection of M2-macrophages in uveal melanoma and relation with survival.Invest Ophthalmol Vis Sci. 2011; 52: 643-650
- Perturbation of lamellar granule secretion by sodium caprate implicates epidermal tight junctions in lamellar granule function.J Dermatol Sci. 2010; 59: 107-114
- Tight junction regulates epidermal calcium ion gradient and differentiation.Biochem Biophys Res Commun. 2011; 406: 506-511
- Mechanical and metabolic injury to the skin barrier leads to increased expression of murine β-defensin-1, -3, and -14.J Invest Dermatol. 2011; 131: 443-452
- Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice.J Clin Invest. 2007; 117: 3339-3349
Published online: May 28, 2013
Received: December 13, 2012
© 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.