Premium
The antimicrobial protein S100A7/psoriasin enhances the expression of keratinocyte differentiation markers and strengthens the skin's tight junction barrier
Author(s) -
Hattori F.,
Kiatsuraya C.,
Okumura K.,
Ogawa H.,
Ikeda S.,
Okamoto K.,
Niyonsaba F.
Publication year - 2014
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.13125
Subject(s) - skin barrier , keratinocyte , antimicrobial , microbiology and biotechnology , protein expression , tight junction , biology , medicine , dermatology , biochemistry , in vitro , gene
Summary Background S100A7/psoriasin is a member of the S100 protein family and is encoded in the epidermal differentiation complex, which contains genes for markers of epidermal differentiation. S100A7/psoriasin is overexpressed in hyperproliferative skin diseases, where it is believed not only to exhibit antimicrobial functions, but also to induce immunomodulatory activities, including chemotaxis and cytokine/chemokine production. Objectives To evaluate the effect of S100A7/psoriasin on keratinocyte differentiation and regulation of the tight junction ( TJ ) barrier. Methods Expression of differentiation markers and TJ proteins in human keratinocytes was determined by real‐time polymerase chain reaction and Western blot. The changes in TJ barrier function were assessed by transepithelial electrical resistance and paracellular permeability assays. Glycogen synthase kinase‐3 ( GSK ‐3) and mitogen‐activated protein kinase ( MAPK ) activation was analysed by Western blot, whereas β‐catenin and E‐cadherin activation was evaluated by Western blot and immunofluorescence. Results S100A7/psoriasin enhanced the expression of several differentiation markers and selectively increased the expression of TJ proteins (e.g. claudins and occludin), which are known to strengthen the TJ barrier. Furthermore, S100A7/psoriasin increased β‐catenin and E‐cadherin accumulation at cell–cell contact, and enhanced transepithelial electrical resistance while reducing the paracellular permeability of keratinocyte layers. The data suggest that S100A7/psoriasin‐mediated regulation of the TJ barrier was via both the GSK ‐3 and MAPK pathways, as evidenced by the inhibitory effects of inhibitors for GSK ‐3 and MAPK s. Conclusions Our finding that S100A7/psoriasin regulates differentiation and strengthens TJ barrier function provides novel evidence that, in addition to antimicrobial and immunoregulatory activities, S100A7/psoriasin is involved in skin innate immunity.