Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light

doi:10.1084/jem.172.6.1609

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Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light

A Kock, T Schwarz, R Kirnbauer, A Urbanski, P Perry, JC Ansel and TA Luger
Department of Dermatology II, University of Vienna, Austria.

Tumor necrosis factor alpha (TNF-alpha), in addition to being cytotoxic for certain tumor cells, has turned out as a multifunctional cytokine that is involved in the regulation of immunity and inflammation. Since human keratinocytes have been demonstrated to be a potent source of various cytokines, it was investigated whether epidermal cells synthesize and release TNF-alpha. Supernatants derived from normal human keratinocytes (HNK) and human epidermoid carcinoma cell lines (KB, A431) were tested both in a TNF-alpha-specific ELISA and a bioassay. In supernatants of untreated epidermal cells, no or minimal TNF-alpha activity was found, while after stimulation with lipopolysaccharide (LPS) or ultraviolet (UV) light, significant amounts were detected. Western blot analysis using an antibody directed against human TNF-alpha revealed a molecular mass of 17 kD for keratinocyte- derived TNF-alpha. These biological and biochemical data were also confirmed by Northern blot analysis revealing mRNA specific for TNF- alpha in LPS- or ultraviolet B (UVB)-treated HNK and KB cells. In addition, increased TNF-alpha levels were detected in the serum obtained from human volunteers 12 and 24 h after a single total body UVB exposure, which caused a severe sunburn reaction. These findings indicate that keratinocytes upon stimulation are able to synthesize and release TNF-alpha, which may gain access to the circulation. Thus, TNF- alpha in concert with other epidermal cell-derived cytokines may mediate local and systemic inflammatory reactions during host defense against injurious events caused by microbial agents or UV irradiation.
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Zhang, Q., Southall, M. D., Mezsick, S. M., Johnson, C., Murphy, R. C., Konger, R. L., Travers, J. B. (2005). Epidermal Peroxisome Proliferator-activated Receptor {gamma} as a Target for Ultraviolet B Radiation. J. Biol. Chem. 280: 73-79 [Abstract] [Full Text]
Banno, T., Gazel, A., Blumenberg, M. (2004). Effects of Tumor Necrosis Factor-{alpha} (TNF{alpha}) in Epidermal Keratinocytes Revealed Using Global Transcriptional Profiling. J. Biol. Chem. 279: 32633-32642 [Abstract] [Full Text]
Kolgen, W., van Meurs, M., Jongsma, M., van Weelden, H., Bruijnzeel-Koomen, C. A. F. M., Knol, E. F., van Vloten, W. A., Laman, J., de Gruijl, F. R. (2004). Differential Expression of Cytokines in UV-B-Exposed Skin of Patients With Polymorphous Light Eruption: Correlation With Langerhans Cell Migration and Immunosuppression. Arch Dermatol 140: 295-302 [Abstract] [Full Text]
Krueger, G., Callis, K. (2004). Potential of Tumor Necrosis Factor Inhibitors in Psoriasis and Psoriatic Arthritis. Arch Dermatol 140: 218-225 [Abstract] [Full Text]
Zhang, J. Y., Green, C. L., Tao, S., Khavari, P. A. (2004). NF-{kappa}B RelA opposes epidermal proliferation driven by TNFR1 and JNK. Genes Dev. 18: 17-22 [Abstract] [Full Text]
Chimienti, F., Hogg, R. C., Plantard, L., Lehmann, C., Brakch, N., Fischer, J., Huber, M., Bertrand, D., Hohl, D. (2003). Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda. Hum Mol Genet 12: 3017-3024 [Abstract] [Full Text]
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Basile, J. R., Eichten, A., Zacny, V., Munger, K. (2003). NF-{kappa}B-Mediated Induction of p21Cip1/Waf1 by Tumor Necrosis Factor {alpha} Induces Growth Arrest and Cytoprotection in Normal Human Keratinocytes. Mol Cancer Res 1: 262-270 [Abstract] [Full Text]
Uchida, T., Suto, H., Ra, C., Ogawa, H., Kobata, T., Okumura, K. (2002). Preferential expression of Th2-type chemokine and its receptor in atopic dermatitis. Int Immunol 14: 1431-1438 [Abstract] [Full Text]
Dawe, R. S., Cameron, H., Yule, S., Man, I., Ibbotson, S. H., Ferguson, J. (2002). UV-B Phototherapy Clears Psoriasis Through Local Effects. Arch Dermatol 138: 1071-1076 [Abstract] [Full Text]
She, Q.-B., Ma, W.-Y., Zhong, S., Dong, Z. (2002). Activation of JNK1, RSK2, and MSK1 Is Involved in Serine 112 Phosphorylation of Bad by Ultraviolet B Radiation. J. Biol. Chem. 277: 24039-24048 [Abstract] [Full Text]
Khaskhely, N. M., Maruno, M., Uezato, H., Takamiyagi, A., Ramzi, S. T., Kasem, K. M. A., Kariya, K.-i., Toda, T., Hashiguchi, Y., Landires, E. A. G., Nonaka, S. (2002). Low-Dose UVB Contributes to Host Resistance against Leishmania amazonensis Infection in Mice through Induction of Gamma Interferon and Tumor Necrosis Factor Alpha Cytokines. CVI 9: 677-686 [Abstract] [Full Text]
Mildner, M., Eckhart, L., Lengauer, B., Tschachler, E. (2002). Hepatocyte Growth Factor/Scatter Factor Inhibits UVB-induced Apoptosis of Human Keratinocytes but Not of Keratinocyte-derived Cell Lines via the Phosphatidylinositol 3-Kinase/AKT Pathway. J. Biol. Chem. 277: 14146-14152 [Abstract] [Full Text]
Foltyn, V N, Golan, T D (2001). In vitro ultraviolet irradiation induces pro-inflammatory responses in cells from premorbid SLE mice. Lupus 10: 272-283 [Abstract]
Antonopoulos, C., Cumberbatch, M., Dearman, R. J., Daniel, R. J., Kimber, I., Groves, R. W. (2001). Functional Caspase-1 Is Required for Langerhans Cell Migration and Optimal Contact Sensitization in Mice. J. Immunol. 166: 3672-3677 [Abstract] [Full Text]
Slominski, A., Wortsman, J. (2000). Neuroendocrinology of the Skin. Endocr. Rev. 21: 457-487 [Abstract] [Full Text]
Ruckert, R., Asadullah, K., Seifert, M., Budagian, V. M., Arnold, R., Trombotto, C., Paus, R., Bulfone-Paus, S. (2000). Inhibition of Keratinocyte Apoptosis by IL-15: A New Parameter in the Pathogenesis of Psoriasis?. J. Immunol. 165: 2240-2250 [Abstract] [Full Text]
Petit-Frere, C., Capulas, E., Lyon, D. A., Norbury, C. J., Lowe, J. E., Clingen, P. H., Riballo, E., Green, M. H. L., Arlett, C. F. (2000). Apoptosis and cytokine release induced by ionizing or ultraviolet B radiation in primary and immortalized human keratinocytes. Carcinogenesis 21: 1087-1095 [Abstract] [Full Text]
Liebler, D. C., Burr, J. A. (2000). Effects of UV light and tumor promoters on endogenous vitamin E status in mouse skin. Carcinogenesis 21: 221-225 [Abstract] [Full Text]
Imaizumi, T., Itaya, H., Fujita, K., Kudoh, D., Kudoh, S., Mori, K., Fujimoto, K., Matsumiya, T., Yoshida, H., Satoh, K. (2000). Expression of Tumor Necrosis Factor-{alpha} in Cultured Human Endothelial Cells Stimulated With Lipopolysaccharide or Interleukin-1{alpha}. Arterioscler. Thromb. Vasc. Bio. 20: 410-415 [Abstract] [Full Text]
Darmstadt, G. L., Mentele, L., Fleckman, P., Rubens, C. E. (1999). Role of Keratinocyte Injury in Adherence of Streptococcus pyogenes. Infect. Immun. 67: 6707-6709 [Abstract] [Full Text]
Nakagawa, S., Koomen, C. W., Bos, J. D., Teunissen, M. B. M. (1999). Differential Modulation of Human Epidermal Langerhans Cell Maturation by Ultraviolet B Radiation. J. Immunol. 163: 5192-5200 [Abstract] [Full Text]
Kothny-Wilkes, G., Kulms, D., Luger, T. A., Kubin, M., Schwarz, T. (1999). Interleukin-1 Protects Transformed Keratinocytes from Tumor Necrosis Factor-related Apoptosis-inducing Ligand- and CD95-induced Apoptosis but Not from Ultraviolet Radiation-induced Apoptosis. J. Biol. Chem. 274: 28916-28921 [Abstract] [Full Text]
Zaretzky, F. R., Kawula, T. H. (1999). Examination of Early Interactions between Haemophilus ducreyi and Host Cells by Using Cocultured HaCaT Keratinocytes and Foreskin Fibroblasts. Infect. Immun. 67: 5352-5360 [Abstract] [Full Text]
Dy, L. C., Pei, Y., Travers, J. B. (1999). Augmentation of Ultraviolet B Radiation-induced Tumor Necrosis Factor Production by the Epidermal Platelet-activating Factor Receptor. J. Biol. Chem. 274: 26917-26921 [Abstract] [Full Text]
Corsini, E., Battaini, F., Lucchi, L., Marinovich, M., Racchi, M., Govoni, S., Galli, C. L. (1999). A Defective Protein Kinase C Anchoring System Underlying Age-Associated Impairment in TNF-{alpha} Production in Rat Macrophages. J. Immunol. 163: 3468-3473 [Abstract] [Full Text]
Arnold, R., Seifert, M., Asadullah, K., Volk, H. D. (1999). Crosstalk Between Keratinocytes and T Lymphocytes via Fas/Fas Ligand Interaction: Modulation by Cytokines. J. Immunol. 162: 7140-7147 [Abstract] [Full Text]
Soriani, M., Luscher, P., Tyrrell, R. M. (1999). Direct and indirect modulation of ornithine decarboxylase and cyclooxygenase by UVB radiation in human skin cells. Carcinogenesis 20: 727-732 [Abstract] [Full Text]
Catania, R. A., Schwacha, M. G., Cioffi, W. G., Bland, K. I., Chaudry, I. H. (1999). Does Uninjured Skin Release Proinflammatory Cytokines Following Trauma and Hemorrhage?. Arch Surg 134: 368-374 [Abstract] [Full Text]
Zhuang, L., Wang, B., Shinder, G. A., Shivji, G. M., Mak, T. W., Sauder, D. N. (1999). TNF Receptor p55 Plays a Pivotal Role in Murine Keratinocyte Apoptosis Induced by Ultraviolet B Irradiation. J. Immunol. 162: 1440-1447 [Abstract] [Full Text]
Yoshida, Y., Kang, K., Berger, M., Chen, G., Gilliam, A. C., Moser, A., Wu, L., Hammerberg, C., Cooper, K. D. (1998). Monocyte Induction of IL-10 and Down-Regulation of IL-12 by iC3b Deposited in Ultraviolet-Exposed Human Skin. J. Immunol. 161: 5873-5879 [Abstract] [Full Text]
Farrell, A. M., Uchida, Y., Nagiec, M. M., Harris, I. R., Dickson, R. C., Elias, P. M., Holleran, W. M. (1998). UVB irradiation up-regulates serine palmitoyltransferase in cultured human keratinocytes. J. Lipid Res. 39: 2031-2038 [Abstract] [Full Text]
Barber, L. A., Spandau, D. F., Rathman, S. C., Murphy, R. C., Johnson, C. A., Kelley, S. W., Hurwitz, S. A., Travers, J. B. (1998). Expression of the Platelet-activating Factor Receptor Results in Enhanced Ultraviolet B Radiation-induced Apoptosis in a Human Epidermal Cell Line. J. Biol. Chem. 273: 18891-18897 [Abstract] [Full Text]
Aragane, Y., Kulms, D., Metze, D., Wilkes, G., Poppelmann, B., Luger, T. A., Schwarz, T. (1998). Ultraviolet Light Induces Apoptosis via Direct Activation of CD95 (Fas/APO-1) Independently of Its Ligand CD95L. JCB 140: 171-182 [Abstract] [Full Text]
Aragane, Y., Kulms, D., Luger, T. A., Schwarz, T. (1997). Down-regulation of interferon gamma -activated STAT1 by UV�light. Proc. Natl. Acad. Sci. USA 94: 11490-11495 [Abstract] [Full Text]
Sadeh, J. S., Rudikoff, D., Gordon, M. L., Bowden, J., Goldman, B. D., Lebwohl, M. (1997). Pustular and Erythrodermic Psoriasis Complicated by Acute Respiratory Distress Syndrome. Arch Dermatol 133: 747-750 [Abstract]
Bennion, S., Norns, D. (1997). Ultraviolet light modulation of autoantigens, epidermal cytokines and adhesion molecules as contributing factors of the pathogenesis of cutaneous LE. Lupus 6: 181-192
Rosette, C., Karin, M. (1996). Ultraviolet Light and Osmotic Stress: Activation of the JNK Cascade Through Multiple Growth Factor and Cytokine Receptors. Science 274: 1194-1197 [Abstract] [Full Text]
Brauchle, M., Funk, J., Kind, P., Werner, S. (1996). Ultraviolet B and H2O2 Are Potent Inducers of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes. J. Biol. Chem. 271: 21793-21797 [Abstract] [Full Text]
Cheng, J, Turksen, K, Yu, Q C, Schreiber, H, Teng, M, Fuchs, E (1992). Cachexia and graft-vs.-host-disease-type skin changes in keratin promoter-driven TNF alpha transgenic mice.. Genes Dev. 6: 1444-1456 [Abstract]
Kulms, D., Schwarz, T. (2001). Ultraviolet Radiation Inhibits Interleukin-2-induced Tyrosine Phosphorylation and the Activation of STAT5 in T Lymphocytes. J. Biol. Chem. 276: 12849-12855 [Abstract] [Full Text]