title: Distribution of dipeptidyl-peptidase IV on keratinocytes in the margin zone of a psoriatic lesion: a comparison with hyperproliferation and aberrant differentiation markers.
abstract: The inflammation process in psoriatic skin is characterized by influx of leukocytes, hyperproliferation and aberrant differentiation of keratinocytes regulated via cytokines. Dipeptidyl-peptidase IV (DPPIV) is known to be upregulated on keratinocytes in the psoriatic lesion. The objective was to gain insight into dynamics of DPPIV expression and enzyme activity together with keratinocyte proliferation and differentiation markers during development of a psoriatic lesion, in order to investigate coherence in mechanisms behind the upregulation of DPPIV in psoriatic skin. The expression of DPPIV, Ki-67 antigen and keratin-16 (K16) was studied in the dynamic margin zone of the psoriatic lesion, examining skin sections of the clinically uninvolved skin, the early lesion and the chronic lesion of psoriatic patients compared to healthy volunteers using immunohistochemical and enzymehistochemical staining methods. DPPIV-expression and enzyme activity, Ki-67 antigen and K16 are significantly upregulated in the centre and inner margin of the lesion compared to clinically uninvolved skin and the healthy volunteers skin. Mutually between the centre and inner margin, this upregulation did not differ significantly. The clinical symptomless skin proved to have significantly elevated DPPIV enzyme activity compared to the skin of healthy volunteers. We demonstrate that DPPIV is expressed and enzymatically active well before the development of an overt psoriatic lesion. The abnormal DPPIV distribution in psoriatic skin does not coincide with known markers of aberrant growth and differentiation of keratinocytes, which makes DPPIV (expression and enzyme activity) a marker standing on its own.
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. r.vanlingen@derma.umcn.nl
authors.forename: R G
authors.initials: RG
authors.lastname: van Lingen
authors.forename: M K P
authors.initials: MK
authors.lastname: Poll
authors.forename: M M B
authors.initials: MM
authors.lastname: Seyger
authors.forename: E M G J
authors.initials: EM
authors.lastname: de Jong
authors.forename: P C M
authors.initials: PC
authors.lastname: van de Kerkhof
authors.forename: P E J
authors.initials: PE
authors.lastname: van Erp
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D053536:Keratin-16 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D053536:Keratin-16; D019394:Ki-67 Antigen; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4