title: Expression of serine protease inhibitors in epidermal keratinocytes is increased by calcium but not 1,25-dihydroxyvitamin D3or retinoic acid.
abstract: BACKGROUND
  In human skin, the serine proteases kallikrein-related peptidase (KLK)5 and KLK7 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 SPINK5; secretory leucocyte peptidase inhibitor (SLPI); and elafin. Expression of KLK5 and KLK7 is controlled and upregulated by stimulants such as calcium, 1,25-dihydroxyvitamin D3[1,25(OH)2VD3] and retinoic acid (RA).
  
  
  OBJECTIVE
  To understand the effect of calcium, 1,25(OH)2VD3and RA on the expression of serine protease inhibitors in epidermal keratinocytes.
  
  
  METHODS
  We stimulated normal human epidermal keratinocytes (NHEKs) with high calcium, 1,25(OH)2VD3or 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 NHEKs.
  
  
  RESULTS
  High calcium, but not 1,25(OH)2VD3or RA, significantly induced the expression of LEKTI, SLPI and elafin at both transcript and protein levels in NHEKs. 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 NHEKs.
  
  
  CONCLUSIONS
  High calcium, but not 1,25(OH)2VD3or 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.
authors: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: M
authors: M
authors: Kobashi
authors: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: S
authors: S
authors: Morizane
authors: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: S
authors: S
authors: Sugimoto
authors: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: S
authors: S
authors: Sugihara
authors: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: K
authors: K
authors: Iwatsuki
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D053818:Chymases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D053492:Elafin / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D007641:Keratolytic Agents / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D000074163:Serine Peptidase Inhibitor Kazal-Type 5 / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation; D014815:Vitamins / Q000494:pharmacology
chemical_list: D053492:Elafin; D007641:Keratolytic Agents; C506806:PI3 protein, human; C506814:SLPI protein, human; C120650:SPINK5 protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors; D014815:Vitamins; C114880:trypsin-like serine protease; D014212:Tretinoin; D012697:Serine Endopeptidases; D053818:Chymases; D002117:Calcitriol; D002118:Calcium