title: Altered claudin expression is a feature of chronic plaque psoriasis.
abstract: Epithelial tight junctions play a central role in cell-cell adhesion and are necessary for the selective paracellular movement of ions. Claudins are key components of tight junctions and their expression is altered in gut epithelia in a variety of inflammatory enteropathies, including ulcerative colitis and Crohn's disease. Psoriasis is a chronic inflammatory skin disease affecting approximately 2% of the western population, with significantly increased occurrence in individuals with Crohn's disease. Initial studies investigated the expression of claudins in skin of healthy volunteers and patients with chronic plaque psoriasis. We report here that claudins-1 and -3 are the major protein species present in the epidermis of healthy skin; they are expressed on the surface of epidermal keratinocytes, consistent with their localization to tight junctions. In plaques of psoriasis, claudin-1 was not identifiable in the epidermis, although typical staining patterns were observed in clinically normal, uninvolved skin of patients with psoriasis. Claudin-3 was present in the epidermal granular cell layer in normal skin, but was only identified within the cytosol of epidermal keratinocytes in both involved and uninvolved skin of psoriasis patients. We examined further whether exposure of keratinocytes in vitro to pro-inflammatory cytokines mimicked the observed changes in claudin expression seen in chronic plaque psoriasis; lipopolysaccharide, interferon-gamma and tumour necrosis factor-alpha had no effect on claudin protein expression or distribution. Addition of interleukin-1beta, however, resulted in down-regulation of claudins-1 and -3. Tumour necrosis factor-alpha and interleukin-1beta were further used in an in vivo model of skin inflammation; interleukin-1beta alone modulated claudin protein expression in this system. These data demonstrate that epidermal claudin expression is altered in chronic plaque psoriasis and that expression is in part modulated by interleukin-1beta.
authors.affiliation: Dermatological Sciences Research Group, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK. rachel.watson@manchester.ac.uk
authors.forename: R E B
authors.initials: RE
authors.lastname: Watson
authors.forename: R
authors.initials: R
authors.lastname: Poddar
authors.forename: J M
authors.initials: JM
authors.lastname: Walker
authors.forename: I
authors.initials: I
authors.lastname: McGuill
authors.forename: L M
authors.initials: LM
authors.lastname: Hoare
authors.forename: C E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: C A
authors.initials: CA
authors.lastname: O'neill
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D062445:Claudin-1; D062465:Claudin-3; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; D062445:Claudin-1; D062465:Claudin-3; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008565:Membrane Proteins