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Expression of serine protease inhibitors in epidermal keratinocytes is increased by calcium but not 1,25‐dihydroxyvitamin D 3 or retinoic acid
Author(s) -
Kobashi M.,
Morizane S.,
Sugimoto S.,
Sugihara S.,
Iwatsuki K.
Publication year - 2017
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.15153
Subject(s) - proteases , elafin , serine protease , serine , kallikrein , chemistry , biochemistry , protease , antipain , microbiology and biotechnology , trypsin , slpi , leupeptin , enzyme , biology , immunology , inflammation
Summary Background In human skin, the serine proteases kallikrein‐related peptidase ( KLK )5 and KLK 7 degrade corneodesmosome proteins, leading to desquamation. Serine protease activity of the skin is tightly regulated by the interplay between such proteases and serine protease inhibitors, including lymphoepithelial Kazal‐type related inhibitor ( LEKTI ), encoded by SPINK 5 ; secretory leucocyte peptidase inhibitor ( SLPI ); and elafin. Expression of KLK 5 and KLK 7 is controlled and upregulated by stimulants such as calcium, 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 VD 3 ] and retinoic acid ( RA ). Objectives To understand the effect of calcium, 1,25(OH) 2 VD 3 and RA on the expression of serine protease inhibitors in epidermal keratinocytes. Methods We stimulated normal human epidermal keratinocytes ( NHEK s) with high calcium, 1,25(OH) 2 VD 3 or RA , and then analysed the expression of serine protease inhibitors using quantitative real‐time polymerase chain reaction, enzyme‐linked immunosorbent assay and immunocytofluorescence. We also analysed trypsin‐ and chymotrypsin‐like serine protease activities in stimulated NHEK s. Results High calcium, but not 1,25(OH) 2 VD 3 or RA , significantly induced the expression of LEKTI , SLPI and elafin at both transcript and protein levels in NHEK s. These inductions were time‐ and dose‐dependent. The activities of trypsin‐ and chymotrypsin‐like serine proteases were significantly up‐ and downregulated by high calcium, respectively, in NHEK s. Conclusions High calcium, but not 1,25(OH) 2 VD 3 or RA , increases the expression of serine protease inhibitors in epidermal keratinocytes. Our findings contribute to the understanding of the mechanisms by which serine protease activities are regulated by serine proteases and related inhibitors in epidermal keratinocytes.