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Cannabinoid receptors 1 and 2 oppositely regulate epidermal permeability barrier status and differentiation
Author(s) -
Roelandt Truus,
Heughebaert Carol,
Bredif Stephanie,
Giddelo Christina,
Baudouin Caroline,
Msika Philippe,
Roseeuw Diane,
Uchida Yoshikazu,
Elias Peter M.,
Hachem JeanPierre
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2012.01561.x
Subject(s) - filaggrin , involucrin , loricrin , endocrinology , microbiology and biotechnology , chemistry , cannabinoid receptor , barrier function , medicine , receptor , biology , keratinocyte , agonist , immunology , biochemistry , in vitro , atopic dermatitis
Cannabinoid receptors ( CBR ) 1 and 2 have been implicated in keratinocyte differentiation/proliferation. How CB receptors affect epidermal permeability barrier and stratum corneum structure and function remains unclear. Permeability barrier abrogation was induced by sequential tape‐stripping of the SC and assessed in both CB 1 R and CB 2 R knockout (−/−) mice in comparison with wild‐type (+/+) littermates. Absence of CB 1 R delays permeability barrier recovery, while the latter was found to be accelerated in CB 2 R −/− mice. While increased lamellar body ( LB ) secretion is observed in CB 2 R −/− mice accounting for the enhanced recovery, CB 1 R −/− animals display strong alterations in lipid bilayer structures. Markers for epidermal differentiation (i.e. filaggrin, loricrin and involucrin) and terminal differentiation (i.e. TUNEL assay and caspase‐14 activation) were respectively decreased and increased in CB 1 R and CB 2 R −/− mice. Surprisingly, CB 1 R agonist treatment of human cultured keratinocytes increases mRNA of p21 and cytokeratin 1 and 10 and decreases cyclin D 1 but protein levels remained unchanged. Such paradox could partially be explained by the increase in non‐phosphorylated‐4 E ‐ BP 1, an inhibitor of mRNA translation, following CB 1 R agonist treatment. Altogether, these observations put forward the importance and the complexity of cannabinoid signalling for the regulation of permeability barrier and epidermal differentiation.