Normal response to tumor necrosis factor-alpha and transforming growth factor-beta by keratinocytes in psoriasis.
Normal and chronic plaque psoriatic keratinocyte cultures were tested for their in vitro response to 2-200 ng/ml TNF-alpha and 0.1-10 ng/ml TGF-beta in a serum-free culture system. All normal and lesional psoriatic epidermal cell cultures showed a dose- and time-dependent inhibition of growth in response to TNF-alpha and TGF-beta. Inhibition in individual cultures was first seen at a concentration of 2 ng/ml for TNF-alpha and 0.1 ng/ml for TGF-beta at day 2, but became significant at 20 ng/ml and 1 ng/ml for TNF-alpha and TGF-beta respectively at days 2-6. This effect was statistically significant at days 3-4 for the group of normal (TNF-alpha and TGF-beta, n = 10, p < 0.01) and psoriatic cultures (TNF-alpha, n = 9, p < 0.01; TGF-beta, 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 keratinocytes and in the upper 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 dermis. This study has shown that the growth of normal and psoriatic keratinocytes was equally inhibited by TNF-alpha and TGF-beta in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Malkani
A K
AK
Dept. of Dermatology, St Mary's Hospital, Paddington, London, U.K.
Baker
B S
BS
Garioch
J J
JJ
Powles
A V
AV
Lewis
H M
HM
Valdimarsson
H
H
Fry
L
L
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D011565:Psoriasis / Q000473:pathology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D009687:Nuclear Proteins; D018124:Receptors, Tumor Necrosis Factor; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha