The large T antigen of SV40 (LT) has been widely used to immortalize primary cells for various studies. In this study, synovial fibroblasts of a patient from rheumatoid arthritis (RA) were transformed with LT gene to analyze the effect of SV40-mediated transformation on the production of cytokines, such as IL-6, IL-8, and GM-CSF, that are under the control of interleukin-1β (IL-1β), a physiological inducer of nuclear factor κB (NF-κB). It was noted that the basal levels of GM-CSF and IL-8 were upregulated, whereas that of IL-6 was downregulated. Moreover, the extents of induction of these cytokines in response to IL-1β were markedly downregulated in synovial fibroblasts transformed by LT as compared from parental cells. Although IL-1β could translocate NF-κB to the nucleus in all cells, some of the transformed cells exhibited nuclear translocation of NF-κB even before the stimulation with IL-1β, suggesting that transformation of LT resulted in the constitutive activation of NF-κB, either directly or indirectly. In order to examine whether LT downregulate the κB-dependent gene expression, we performed the transient luciferase gene expression assay. We found that co-transfection of LT did not downregulate the κB-dependent gene expression that was stimulated with L-1β. These observations suggest that the apparent inhibitory effect of LT on the IL-1-induced expression of cytokines may not be through its direct action on the NF-κB transactivation.
Archives of Virology – Springer Journals
Published: Feb 1, 1999
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
All the latest content is available, no embargo periods.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud