Nature Genetics
10, 161 - 166 (1995)
doi:10.1038/ng0695-161
Cytokine gene expression in epidermis with biological effects following injection of naked DNAUlrich R. Hengge1, Edward F. Chan1, Ruth A. Foster1, Patricia S. Walker1
& Jonathan C. Vogel1
1Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA Correspondence should be addressed to J.C.V. The epidermis is readily accessible for genetic manipulation and is easily monitored. Using pig skin because it is very similar to human skin morphologically, we have developed a method to transiently express biologically active factors in epidermis. Following direct injection of naked plasmid DNA into skin, DNA is taken up and transiently expressed at high levels by epidermal keratinocytes. Injection of interleukin−8 plasmid DNA into skin results in the appropriate biological response of neutrophil recruitment, demonstrating functional utility. In addition to this model's therapeutic uses, the biological effects of structural gene products on the epidermis could also be studied in vivo.
REFERENCES
- Vogel, J.C. Keratinocyte gene therapy. Arch. Derm. 129, 1478–1483 (1993). | Article | PubMed | ISI | ChemPort |
- Fenjves, E.S. et al. in DNA Damage and Repair in Human Tissues (eds Sutherland, B.M. & Woodhead, A.D.) 215–223 (Plenum Press, New York, 1990). | ChemPort |
- Fenjves, E.S., Gordan, D.A., Pershing, L.K., Williams, D.L. & Taichman, L.B. Systemic distribution of apolipoprotein E secreted by grafts of epidermal keratinocytes: Implications for epidermal function and gene therapy. Proc. Natl. Acad. Sci. U.S.A. 86, 8803–8807 (1989). | PubMed | ChemPort |
- Gerrard, A.J., Hudson, D.L., Brownlee, G.G. & Watt, F.M. Towards gene therapy for hemophilia B using primary human keratinocytes. Nature Genet. 3, 180–183 (1993). | Article | PubMed | ISI | ChemPort |
- Flowers, M.E.D. et al. Long-term transplantation of canine keratinocytes made resistant to G418 through retrovirus-mediated gene transfer. Proc. Natl. Acad. Sci. U.S.A. 87, 2349–2353 (1990). | PubMed | ChemPort |
- Morgan, J.R., Barrandon, Y., Green, H. & Mulligan, R.C. Expression of an exogenous growth hormone gene by transplantable human epidermal cells. Science 237, 1476–1479 (1987). | PubMed | ISI | ChemPort |
- Uitto, J. & Christiano, A.M. Molecular genetics of the cutaneous basement membrane zone. Perspectives on epidermolysis bullosa and other blistering skin diseases. J. Clin. Invest. 90, 687–692 (1992). | PubMed | ISI | ChemPort |
- Baron, S. et al. ,. The interferons. Mechanisms of action and clinical applications. J. Am. med. Assoc. 266, 1375–1383 (1991). | Article | ISI | ChemPort |
- Pardoll, D.M. Cancer vaccines. Immun. Today 14, 310–316 (1993). | Article | PubMed | ISI | ChemPort |
- Tang, D., DeVit, M. & Johnston, S.A. Genetic immunization is a simple method for eliciting and immune response. Nature 356, 152–154 (1992). | Article | PubMed | ISI | ChemPort |
- Fynan, E.F., Webster, R.G., Fuller, D.H., Haynes, J.R. & Santoro, J.C. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Natl. Acad. Sci. U.S.A. 90, 11478–11482 (1993). | PubMed | ChemPort |
- Raz, E. et al. Intradermal gene immunization: The possible role of DNA uptake in the induction of cellular immunity to viruses. Proc. Natl. Acad. Sci. U.S.A. 91, 9519–9523 (1994). | PubMed | ChemPort |
- Kangesu, T. et al. A porcine model using skin graft chambers for studies on cultured keratinocytes. Br. J. plast. Surg. 46, 393–400 (1993). | ChemPort |
- Wolff, J.A. et al. Direct gene transfer into mouse muscle In vivo. Science 247, 1465–1468 (1990). | PubMed | ISI | ChemPort |
- Leonard, E.J., Yoshimura, T., Tanaka, S. & Raffeld, M. Neutrophil recruitment by intradermally injected neutrophil attractant/activation protein-1. J. invest Derm. 96, 690–694 (1991). | PubMed | ISI | ChemPort |
- Rot, A. Chemotactic potency of recombinant human neutrophil attractant/ activation protein-1 (interleukin-8) for polymorphonuclear leukocytes of different species. Cytokine 3, 21–27 (1991). | Article | PubMed | ISI | ChemPort |
- Wolff, J.A., Ludtke, J.J., Acsadi, G., Williams, P. & Jani, A. Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. molec. Genet. 1, 363–369 (1992). | PubMed | ChemPort |
- Anderson, R.G.W., Kamen, B.A., Rothberg, K.G. & Lacey, S.W. Potocytosis: sequestration and transport of small molecules by caveolae. Science 255, 410–411 (1992). | PubMed | ISI | ChemPort |
- Wolff, J.A. et al. Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle. J. Cell Sci. 103, 1249–1259 (1992). | PubMed | ISI | ChemPort |
- Ulmer, J.B. et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259, 1745–1749 (1993). | PubMed | ISI | ChemPort |
- Wang, B. et al. Gene inoculation generates immune responses against human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. U.S.A. 90, 4156–4160 (1993). | PubMed | ChemPort |
- Cox, G.J.M., Zamb, T.J. & Babiuk, L.A. Bovine herpesvirus 1: Immune responses in mice and cattle injected with plasmid DNA. J. Virol. 67, 5664–5667 (1993). | PubMed | ISI | ChemPort |
- Yang, N., Burkholder, J., Roberts, B., Martinell, B. & McCabe, D. In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc. Natl. Acad. Sci. U.S.A. 87, 9568–9572 (1990). | PubMed | ChemPort |
- Williams, R.S. et al. Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles. Proc. Natl. Acad. Sci. U.S.A. 88, 2726–2730 (1991). | PubMed | ChemPort |
- Fuchs, E. Epidermal differentiation: The bare essentials. J. Cell Biol. 111, 2807–2814 (1990). | Article | PubMed | ISI | ChemPort |
- Schwarz, M.A., Owaribe, K., Kartenbeck, J. & Franke, W.W. Desmosomes and hemidesmosomes: constitutive molecular components. A. Rev. Cell Biol. 6, 461–491 (1990). | ISI | ChemPort |
- MacGregor, G.R. & Caskey, C.T. Construction of plasmids that express E.colli
 -galactosidase in mammalian cells. Nucl. Acids Res. 17, 2365 (1989). | PubMed | ISI | ChemPort |
- Matsushima, K. et al. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J. exp. Med. 167, 1883–1893 (1988). | PubMed | ISI | ChemPort |
- Cotten, M., Baker, A., Saltik, M., Wagner, E. & Buschle, M. Lipopolysaccharide is a frequent contaminant of plasmid DNA preparations and can be toxic to primary human cells in the presence of adenovirus. Gene Ther. 1, 239–246 (1994). | PubMed | ISI | ChemPort |
- Aida, Y. & Pabst, M.J. Removal of endotoxin from protein solutions by phase separation using Triton X-114. J. Immun. Meth. 132, 191–195 (1990). | Article | ISI | ChemPort |
- Jain, V.K. & Magrath, I.T. A chemiluminescent assay for quantitation of -galactosidase in the femtogram range: application to quantitation of -galactosidase in /acZ-transfected cells. Annal. Biochem. 199, 119–124 (1991). | ChemPort |
- Vogel, J., Hinrichs, S.H., Reynolds, R.K., Luciw, P.A. & Jay, G. The HIV faf gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice. Nature 335, 606–611 (1988). | Article | PubMed | ISI | ChemPort |
- Hirt, B. Selective extraction of polyoma DNA from infected mouse cell cultures. J. molec. Biol. 26, 365–369 (1967). | PubMed | ISI | ChemPort |
- Simonet, W.S. et al. Long-term impaired neutrophil migration in mice overexpressing human interleukin-8. J. clin. Invest. 94, 1310–1319 (1994). | PubMed | ISI | ChemPort |
|
