RESUMEN
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.
Asunto(s)
Diferenciación Celular , Proliferación Celular , Dipeptidil Peptidasa 4/metabolismo , Queratina-16/metabolismo , Queratinocitos/metabolismo , Antígeno Ki-67/metabolismo , Psoriasis/metabolismo , Anciano , Biomarcadores/metabolismo , Biopsia , Estudios de Casos y Controles , Dipeptidil Peptidasa 4/genética , Femenino , Humanos , Queratina-16/genética , Queratinocitos/patología , Antígeno Ki-67/genética , Masculino , Persona de Mediana Edad , Psoriasis/patología , Piel/metabolismo , Piel/patología , Regulación hacia ArribaRESUMEN
BACKGROUND: Psoriasis is known to affect 2-3% of the population and can be considered an organ-specific autoimmune disease. CD26/dipeptidyl-peptidase IV (DPP-IV) is a membrane-bound protease with diverse properties. In theory, the expression of CD26/DPP-IV has common grounds with three principal key players of the psoriatic pathogenesis: keratinocytes, T cells and cytokines. OBJECTIVES: To assess CD26/DPP-IV expression in psoriasis in order to expand on the search for complementary biomarkers related to inflammation and proliferation in psoriasis. METHODS: The pattern of expression of CD26/DPP-IV was investigated on the mRNA-, protein- and enzyme-functionality level using immunohistochemical, immunofluorescent and enzyme activity labelling techniques. RESULTS: An 11-fold significant increase of CD26/DPP-IV on the mRNA level was demonstrated in psoriatic epidermal sheets compared with normal skin. Immunohistochemistry on psoriatic sections showed a distinct patchy honeycomb-like CD26/DPP-IV staining in the suprapapillary layers. Moreover, a clearly distinguishable column-like staining pattern throughout the suprabasal compartment along the rete ridges was seen, whereas in normal skin these patterns were absent. Strikingly, CD26/DPP-IV enzyme activity correlated with this immunohistochemical reactivity pattern for the CD26/DPP-IV protein. The T-cell bound expression of CD26/DPP-IV in psoriatic skin was explicitly present, albeit in small quantities. CONCLUSIONS: Our data provide clear evidence for a versatile upregulation of CD26/DPP-IV expression in psoriatic (epi)dermis. Although the exact functional contribution remains speculative, the topographical distribution of this complex multifunctional protein suggests a suitable role as a complementary biomarker in psoriasis.