GM-CSF DNA induces specific patterns of cytokines and chemokines in the skin: Implications for DNA vaccines Journal Article
| Authors: | Perales, M. A.; Fantuzzi, G.; Goldberg, S. M.; Turk, M. J.; Mortazavi, F.; Busam, K.; Houghton, A. N.; Dinarello, C. A.; Wolchok, J. D. |
| Article Title: | GM-CSF DNA induces specific patterns of cytokines and chemokines in the skin: Implications for DNA vaccines |
| Abstract: | Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances immune responses by inducing the proliferation, maturation, and migration of dendritic cells, and the expansion and differentiation of B and T lymphocytes. Similar biological effects have been observed with the use of GM-CSF DNA in mouse models for therapy of cancer and infectious diseases, and its use is currently being investigated in clinical trials in combination with DNA vaccines. To further understand the adjuvant mechanisms of GM-CSF DNA, we examined early events following its administration. We found measurable levels of GM-CSF protein in the skin and muscle, as well as in serum. Measurements of other cytokine and chemokine levels revealed differential expression patterns over time. The early response was characterized by high levels of inflammatory molecules, including IL-1β, IL-6, TNFα, RANTES, MIP-1α and MCP-1, later followed by expression of precursor Th1 cytokines, IL-12 and IL-18, concomitant with IFNγ production. Local production of GM-CSF protein also resulted in the early recruitment of polymorphonuclear cells and later recruitment of mononuclear cells, including dendritic cells. These results have implications for understanding early events in the immune response to DNA vaccines, and provide a basis for development of new approaches to cancer vaccines, including the use of cytokine genes as adjuvants. |
| Keywords: | protein expression; nonhuman; adjuvant therapy; protein blood level; mouse; animals; mice; animal tissue; dendritic cell; granulocyte macrophage colony stimulating factor; interleukin 1beta; animal experiment; inflammation; protein; cell assay; mice, inbred c57bl; skin; cytokine; cytokines; dna; immune response; chemokine; tumor necrosis factor alpha; mononuclear cell; gamma interferon; cancer vaccine; drug mechanism; protein synthesis; interleukin 6; protein induction; cytokine production; neutrophils; dna vaccine; muscle level; th1 cell; monocytes; molecular biology; adjuvants, immunologic; macrophages; protein determination; dna determination; vaccines, dna; interleukin 12; vaccine; monocyte chemotactic protein 1; chemokines; interleukin 18; gm-csf; adjuvant; granulocyte-macrophage colony-stimulating factor; rantes; macrophage inflammatory protein 1alpha; priority journal; article; polymorphonuclear cell |
| Journal Title: | Cytokines Cellular and Molecular Therapy |
| Volume: | 7 |
| Issue: | 3 |
| ISSN: | 1368-4736 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2002-01-01 |
| Start Page: | 125 |
| End Page: | 133 |
| Language: | English |
| DOI: | 10.1080/13684730310000923 |
| PUBMED: | 12850812 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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