title: Topical application of calcitriol alters expression of filaggrin but not keratin K1 in mouse epidermis.
abstract: Calcitriol (1 alpha,25-dihydroxyvitamin D3) and its analogues are antiproliferative agents which promote epidermal differentiation in vitro, possibly reflecting their modes of action in the treatment of psoriasis. We examined the effect of calcitriol on early and late terminal differentiation in mouse epidermis in vivo using an immunofluorescence assay to detect keratin K1 and filaggrin expression. Pulse labelling with the tymidine analogue 5-bromo-2-deoxyuridine (BrdUrd) was performed by intraperitoneal injection of mice immediately or 16 h after a single topical application of 0.72 nmol calcitriol. The BrdUrd labelling index (LI) and keratin K1 or filaggrin expression of postmitotic cell cohorts were scored by paired immunofluorescence staining for up to 72 h after BrdUrd labelling. Calcitriol induced cell proliferation as shown by a 100% increase in the BrdUrd LI 17 h after application. The onset of keratin K1 expression in the postmitotic period was, however, unchanged in both series after calcitriol treatment. Filaggrin expression appeared earlier after calcitriol treatment than in control epidermis, probably reflecting altered cell kinetics with increased epidermal turnover. The results suggest that calcitriol only influences the later stages of the keratinocyte differentiation programme, possibly secondarily to its hyperproliferative effect.
authors.affiliation: Institute of Pathology, Medical Faculty, National Hospital, Rikshospitalet, University of Oslo, Norway.
authors.forename: C
authors.initials: C
authors.lastname: Lützow-Holm
authors.forename: A
authors.initials: A
authors.lastname: Heyden
authors.forename: H S
authors.initials: HS
authors.lastname: Huitfeldt
authors.forename: P
authors.initials: P
authors.lastname: Brandtzaeg
authors.forename: O P
authors.initials: OP
authors.lastname: Clausen
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins / Q000032:analysis*; D015603:Keratinocytes / Q000187:drug effects; D007633:Keratins / Q000032:analysis*; D051379:Mice; D008812:Mice, Hairless
chemical_list: D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D007633:Keratins; D002117:Calcitriol; D001973:Bromodeoxyuridine; D002118:Calcium