PMC:2586094 / 17165-18750
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2586094","sourcedb":"PMC","sourceid":"2586094","source_url":"http://www.ncbi.nlm.nih.gov/pmc/2586094","text":"3.6 The synergism between IFN-γ and TNF-α on LPL gene transcription is not mediated at the level of Sp1/Sp3 DNA binding\nInteractions between cytokines in the regulation of macrophage function are relatively common and our previous studies showed a synergistic action of IFN-γ and TNF-α on the expression of LPL mRNA, protein and enzymatic activity [13]. Because this synergism was mediated at the level of gene transcription [28], we wondered whether this occurred at the level of Sp1/Sp3 binding to the LPL gene. Indeed, a recent study has shown that the suppression of sodium–hydrogen exchanger-3 expression by both IFN-γ and TNF-α is mediated through decreased binding of Sp1 and Sp3 [29]. In addition, the TNF-α-mediated downregulation of murine growth hormone receptor expression has been shown to be due to inhibition of Sp1 and Sp3 binding [30]. EMSA were therefore performed using extracts from J774.2 macrophages that had either been left untreated or exposed to TNF-α, IFN-γ, or both TNF-α and IFN-γ, and radiolabelled oligonucleotides corresponding to the + 9/+ 49 or + 46/+ 90 region of the LPL gene. Several different concentrations of TNF-α, which were active in suppressing another response in the laboratory (C/EBP-α promoter activity in Hep3B cells), did not reduce binding by Sp1/Sp3 (Fig. 8A). In addition, the IFN-γ-mediated reduction in the binding of Sp1/Sp3 was not enhanced by TNF-α (Fig. 8B). The concentrations of these two cytokines used corresponded to those that produced a marked synergism at the level of LPL mRNA expression and enzymatic activity [13].","divisions":[{"label":"Title","span":{"begin":5,"end":120}}],"tracks":[{"project":"2_test","denotations":[{"id":"18793716-9505144-20139074","span":{"begin":350,"end":352},"obj":"9505144"},{"id":"18793716-10909770-20139075","span":{"begin":427,"end":429},"obj":"10909770"},{"id":"18793716-16760259-20139076","span":{"begin":689,"end":691},"obj":"16760259"},{"id":"18793716-11390427-20139077","span":{"begin":849,"end":851},"obj":"11390427"},{"id":"18793716-9505144-20139078","span":{"begin":1581,"end":1583},"obj":"9505144"}],"attributes":[{"subj":"18793716-9505144-20139074","pred":"source","obj":"2_test"},{"subj":"18793716-10909770-20139075","pred":"source","obj":"2_test"},{"subj":"18793716-16760259-20139076","pred":"source","obj":"2_test"},{"subj":"18793716-11390427-20139077","pred":"source","obj":"2_test"},{"subj":"18793716-9505144-20139078","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ecb393","default":true}]}]}}