caa a22 4500 465773516 CHVBK 20180323111935.0 cr unu---uuuuu 170327e19900601xx s 000 0 eng 10.1007/BF00371643 doi (NATIONALLICENCE)springer-10.1007/BF00371643 Tumor necrosis factor-alpha inhibits cell proliferation and induces class II antigens and cell adhesion molecules in cultured normal human keratinocytes in vitro [Elektronische Daten] [M. Detmar, C. Orfanos] Summary: The effects of recombinant human tumor necrosis factor-alpha (TNF) on cell proliferation, cell morphology, and on the expression of class II alloantigens and intercellular adhesion molecule-1 (ICAM-1) were assessed in human keratinocytes cultured in serum-free medium. TNF inhibited cell proliferation in a time- and dose-dependent manner with a minimum effective dose of 10 U/ml and a 50% inhibitory dose of 100 U/ml. However, TNF did not induce cell death, and the growth inhibition induced by TNF was completely reversible after its withdrawal. In vitro combination of TNF with interferon-alpha (IFN-alpha) and IFN-beta resulted in additive growth inhibitory effects, while IFN-gamma enhanced the TNF mediated growth inhibition in a synergistic way. Furthermore, TNF altered the morphology of the growing keratinocytes inducing the appearance of a fusiform, fibroblast-like population. Also, treatment with TNF over 6 days markedly induced the expression of ICAM-1 on the cultured keratinocytes with a minimal effective dose of 10 U/ml, while HLA-DR was only moderately expressed after 1,000 U/ml. TNF did not induce HLA-DQ, but reduced the IFN-gamma induced expression of HLA-DR and HLA-DQ. By immunoelectron microscopy, an intense membrane-bound labeling for ICAM-1 was found after treatment with TNF, clearly pronounced in areas of microvillous membrane protrusions. These results indicate that epidermal keratinocytes are a major target for various biological effects of TNF. We also found that TNF differentially modulates IFN-gamma-induced effects, thus suggesting its potential role in the regulation of inflammatory skin disorders. Springer-Verlag, 1990 Tumor necrosis factor-alpha nationallicence Keratinocyte cultures nationallicence Class II antigens nationallicence Cell Adhesion molecules nationallicence Immunoelectron microscopy nationallicence Detmar M. Department of Dermatology, University Medical Center Steglitz, The Free University of Berlin, Hindenburgdamm 30, D-1000, Berlin 45 aut Orfanos C. Department of Dermatology, University Medical Center Steglitz, The Free University of Berlin, Hindenburgdamm 30, D-1000, Berlin 45 aut Archives of Dermatological Research Springer-Verlag 282/4(1990-06-01), 238-245 0340-3696 282:4<238 1990 282 403 https://doi.org/10.1007/BF00371643 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00371643 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Detmar M. Department of Dermatology, University Medical Center Steglitz, The Free University of Berlin, Hindenburgdamm 30, D-1000, Berlin 45 aut NATIONALLICENCE 700 1- Orfanos C. Department of Dermatology, University Medical Center Steglitz, The Free University of Berlin, Hindenburgdamm 30, D-1000, Berlin 45 aut NATIONALLICENCE 773 0- Archives of Dermatological Research Springer-Verlag 282/4(1990-06-01), 238-245 0340-3696 282:4<238 1990 282 403 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer