Tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) receptors on human normal and scleroderma dermal fibroblasts in vitro.
Interferons alpha and gamma (IFN-alpha, IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) exert different regulatory effects on the proliferation and biosynthetic activities of human dermal fibroblasts. Inasmuch as these cytokines bind to specific receptors in order to exert their activities, the expression of IFN-alpha, IFN-gamma and TNF-alpha receptors on fibroblasts from human adult normal and scleroderma skin cultured in vitro were quantitated. Adsorption was detected by incubating confluent normal and scleroderma fibroblasts with various concentrations of [125I]cytokine. Replicate experiments revealed 19,742 +/- 2057 (Kd = 1.15 x 10(-9) M) TNF-alpha receptors per normal dermal fibroblast and 15,006 +/- 75 (Kd = 6.75 x 10(-10) M) TNF-alpha receptors per scleroderma fibroblast. Cross-linking 125I-TNF-alpha to its receptor on normal and scleroderma fibroblasts revealed 130- and 100-kDa TNF-receptor complexes. Although no quantitative or qualitative differences were detected between these two cell types with regard to receptor numbers, TNF-alpha affinity or receptor protein as detected by radiolabelled TNF-alpha, differences were detected in levels of mRNA specific for TNF-alpha receptors. Northern blot analysis revealed normal fibroblasts to constitutively contain mainly mRNA specific for the 55-kDa TNF receptor and indicate that they are capable of responding to TNF-alpha-induced up-regulation of mRNA specific for the 75 kDa TNF receptor. Scleroderma fibroblasts, however, constitutively contain mRNA for both TNF receptors and fail to respond to TNF-alpha up-regulation of the message for the 75-kDa receptor for TNF.(ABSTRACT TRUNCATED AT 250 WORDS)
Berman
B
B
Dermatology Department, University of California, Davis School of Medicine.
Wietzerbin
J
J
D016207:Cytokines / Q000378:metabolism*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D017471:Receptors, Interferon; D018124:Receptors, Tumor Necrosis Factor; D012594:Scleroderma, Localized / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D016898:Interferon-alpha; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma