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Cytokine and growth factor expression by HTLV-1 Lck-tax transgenic cells in SCID mice.
- Source :
-
AIDS research and human retroviruses [AIDS Res Hum Retroviruses] 2010 May; Vol. 26 (5), pp. 593-603. - Publication Year :
- 2010
-
Abstract
- The Tax protein encoded by HTLV-1 plays a key role in the development of ATL in infected individuals. Our previous studies showed that tax transgenic mice develop disease that is almost identical to human ATL, with widespread organ invasion by lymphomatous cells and the development of leukemia. The same pathology develops rapidly in SCID mice engrafted with cells from the transgenic animals. In the present study, we used this SCID model to analyze the expression levels of several cytokines, growth factors, and adhesion molecules to determine their possible involvement in the development of disease. We showed that Tax expression was undetectable at the protein level in the tax-transformed cells used to inoculate the SCID mice and that these cells displayed constitutive NF-kappaB and Akt activity. We demonstrated significant differences in the levels of circulating PDGF-BB, TNF-alpha, sICAM-1, and sVCAM-1 in inoculated animals. Cell-surface staining of the tax transgenic cells showed that they do not express receptors for any of the upregulated growth factors. Significant differences were not found in the secreted levels of bFGF, MMP9, VEGF, or E-selectin, whereas IL-2, IL-15, IL-6, IL-1beta, and IFN-gamma expression was undetectable. Even though the number of factors analyzed is limited, our study identified TNF-alpha, PDGF-BB, and the adhesion molecules sICAM-1 and sVCAM-1 as factors that may contribute to the high levels of organ infiltration by leukemic cells in this tax transgenic SCID model.
- Subjects :
- Animals
Becaplermin
Cytokines genetics
Disease Models, Animal
Gene Products, tax genetics
Human T-lymphotropic virus 1 genetics
Human T-lymphotropic virus 1 metabolism
Humans
Intercellular Adhesion Molecule-1 genetics
Intercellular Adhesion Molecule-1 metabolism
Intercellular Signaling Peptides and Proteins genetics
Mice
Mice, SCID
Mice, Transgenic
Platelet-Derived Growth Factor genetics
Platelet-Derived Growth Factor metabolism
Proto-Oncogene Proteins c-sis
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha metabolism
Vascular Cell Adhesion Molecule-1 genetics
Vascular Cell Adhesion Molecule-1 metabolism
Cytokines metabolism
Gene Expression Regulation
Gene Products, tax metabolism
Human T-lymphotropic virus 1 pathogenicity
Intercellular Signaling Peptides and Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1931-8405
- Volume :
- 26
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- AIDS research and human retroviruses
- Publication Type :
- Academic Journal
- Accession number :
- 20438380
- Full Text :
- https://doi.org/10.1089/aid.2009.0212