Tumour necrosis factor-alpha does not influence proliferation and differentiation of healthy and psoriatic keratinocytes in a skin-equivalent model.
Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of psoriasis. Its effect on keratinocytes from healthy and psoriatic skin was investigated. The keratinocytes were co-cultured with healthy and psoriatic fibroblasts in skin equivalents and grown in a serum-free medium for 15 days. TNF-alpha was added, or not, on day 12. The expression of differentiation and proliferation markers was investigated with immunohistochemistry. The epidermal growth rate was assessed by the percentage of Ki-67-positive nuclei in the basal layers of the outgrowths, which were all multilayered and orthokeratotic. The expression of the epidermal growth factor receptor, cytokeratin 16, involucrin and filaggrin displayed a hyperproliferative, regenerative pattern. No statistically significant differences in growth rate were found between the groups. These findings indicate a lack of effect of TNF-alpha on proliferation and differentiation in healthy and psoriatic keratinocytes. Further studies are warranted to elucidate the pathophysiological role of TNF-alpha in psoriasis.
Fransson
J
J
Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D000091344:Filaggrin Proteins; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011336:Probability; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D003470:Culture Media; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D014409:Tumor Necrosis Factor-alpha