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Normal response to tumor necrosis factor‐alpha and transforming growth factor‐beta by keratinocytes in psoriasis
Author(s) -
Malkani Angeli K.,
Baker Barbara S.,
Garioch Jennifer J.,
Powles Anne V.,
Lewis Helen M.,
Valdimarsson Helgi,
Fry Lionel
Publication year - 1993
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.1993.tb00037.x
Subject(s) - tumor necrosis factor alpha , cytokine , psoriasis , endocrinology , receptor , transforming growth factor , antibody , keratinocyte , medicine , in vitro , epidermal growth factor , biology , immunology , biochemistry
Normal and chronic plaque psoriatic keralinocyte cultures were tested for their in vitro response to 2–200 ng/nil TNF‐α and 0.1–10 ng/ml TGF‐β in a serum‐free culture system. All normal and lesional psoriatic epidermal cell cultures showed a dose‐ and lime‐dependent inhibition of growth in response to TNF‐α and TGF‐β. Inhibition in individual cultures was first seen at a concentration of 2 ng/ml for TNF‐α and 0.1 ng/ml for TGF‐β at day 2, but became significant at 20 ng/ml and 1 ng/ ml for TNF‐α and TGF‐β respectively at days 2‐6. This effect was statistically significant at days 3–4 for the group of normal (TNF‐α and TGF‐β, n = 10, p<0.01 and psoriatic cultures (TNF‐α. n = 9, p<0.0l; TGF‐β, n = 7, p<0.05). Epidermal cells from normal and psoriatic skin were inhibited to the same extent at the same optimal concentrations by each cytokine. Inhibition was abolished by the addition of specific antibody to each cytokine, whilst antibody to a different cytokine had no effect. Nuclear and/or nuclear membrane staining was observed with antibody to the p55 TNF receptor both in cultured keralinocyles and in the tipper epidermal layers of both normal and psoriatic skin. In contrast, plasma membrane and cytoplasmic expression of the p55 TNF receptor was observed on macrophages and lymphocytes infiltrating psoriatic der‐mis. This study has shown that the growth of normal and psoriatic keratinocytes was equally inhibited by TNF‐α and TGF‐β in vitro . The expression of TNF receptor by psoriatic keratinocytes in vivo may permit regulation of epidermal growth by administration of TNF‐α in this disease.