Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-11-6
pubmed:abstractText
In this study an amphotropic retrovirus has been used to efficiently transduce normal human (NF) and scleroderma (systemic sclerosis; SSc) dermal fibroblasts (SScF) with a sequence encoding a temperature-sensitive mutant of the SV40 large T antigen (tsA58-U19). From the primary outgrowths of skin explants, cultures were generated whose growth was stringently temperature-dependent. When grown at a low, permissive temperature (35 degrees C), both normal and SSc-transduced cells continuously divided with similar doubling times, whereas at a high, nonpermissive temperature (39.5 degrees C), division of both the NF and SScF cells was rapidly arrested. These cells have been passaged more than 50 times, have the typical morphological appearance of fibroblasts, and have retained an anchorage-dependent phenotype. The transduced normal cells (tsT-NF) synthesized the matrix molecules collagen and fibronectin and expressed phenotypic antigens characteristic of their nontransduced counterparts, including MHC Class I, VLA beta 1 (CD29), Hermes 1 (CD44), VLA-4 alpha (CD49d), ICAM-1 (CD54) and LFA-3 (CD58) and the cell surface ectoenzymes neutral endopeptidase (CD10), aminopeptidase N (CD13), and dipeptidyl peptidase IV (CD26). Analysis of the transduced SSc fibroblasts (tsT-SScF) showed that these cells exhibited certain major features of the SSc pathology, notably the abnormally high synthesis of type I collagen, increased expression of ICAM-1, and depressed levels of CD26. Moreover, these phenotypic characteristics were retained even after prolonged culture in vitro. The tsT-SScF cells also retained their responsiveness to cytokines, since interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) both produced a marked increase in ICAM-1 expression. Our findings show that infection of SScF with the SV40 tsT antigen extends the life span of these cells and does not ablate their abnormal phenotypic and functional characteristics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:volume
220
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
407-14
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7556450-Antibodies, pubmed-meshheading:7556450-Antibody Specificity, pubmed-meshheading:7556450-Antigens, Polyomavirus Transforming, pubmed-meshheading:7556450-Cell Adhesion, pubmed-meshheading:7556450-Cell Adhesion Molecules, pubmed-meshheading:7556450-Cell Cycle, pubmed-meshheading:7556450-Cell Division, pubmed-meshheading:7556450-Cells, Cultured, pubmed-meshheading:7556450-Collagen, pubmed-meshheading:7556450-Fibroblasts, pubmed-meshheading:7556450-Fibronectins, pubmed-meshheading:7556450-Gene Expression, pubmed-meshheading:7556450-Histocompatibility Antigens Class I, pubmed-meshheading:7556450-Histocompatibility Antigens Class II, pubmed-meshheading:7556450-Humans, pubmed-meshheading:7556450-Kinetics, pubmed-meshheading:7556450-Major Histocompatibility Complex, pubmed-meshheading:7556450-Phenotype, pubmed-meshheading:7556450-Procollagen, pubmed-meshheading:7556450-Reference Values, pubmed-meshheading:7556450-Scleroderma, Systemic, pubmed-meshheading:7556450-Simian virus 40, pubmed-meshheading:7556450-Skin, pubmed-meshheading:7556450-Temperature, pubmed-meshheading:7556450-Time Factors, pubmed-meshheading:7556450-Transfection
pubmed:year
1995
pubmed:articleTitle
Scleroderma-derived human fibroblasts retain abnormal phenotypic and functional characteristics following retroviral transduction with the SV40 tsT antigen.
pubmed:affiliation
Department of Rheumatology, Royal Free Hospital, London, United Kingdom.
pubmed:publicationType
Journal Article, Comparative Study