| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
136-316 |
DRI_Background |
denotes |
Interferon-gamma (IFN-gamma), a multifunctional cytokine produced by activated Th1 lymphocytes, exerts potent effects on the extracellular matrix by regulating fibroblast function. |
| T2 |
317-434 |
DRI_Approach |
denotes |
In this study, we examined the modulation of alpha1(I) procollagen gene (COL1A1) expression by recombinant IFN-gamma. |
| T3 |
435-691 |
DRI_Outcome |
denotes |
The results showed that IFN-gamma stimulated the rapid accumulation of interferon regulated factor (IRF)-1 mRNA, followed by a delayed and dose-dependent inhibition of alpha1(I) procollagen mRNA expression in skin fibroblasts from several different donors. |
| T4 |
692-798 |
DRI_Outcome |
denotes |
The inhibitory response was abrogated in fibroblasts stably expressing IRF-1 in the antisense orientation. |
| T5 |
799-915 |
DRI_Outcome |
denotes |
A marked decrease in the amount of heterogeneous nuclear pre-mRNA preceded the inhibition of COL1A1 mRNA expression. |
| T6 |
916-959 |
DRI_Background |
denotes |
In fibroblasts transiently transfected with |
| T7 |
992-1134 |
DRI_Background |
denotes |
acetyltransferase reporter gene plasmids, IFN-gamma selectively inhibited promoter activity and abrogated its stimulation induced by TGF-beta. |
| T8 |
1135-1293 |
DRI_Challenge |
denotes |
The inhibition by IFN-gamma was not due to downregulation of TGF-beta receptor mRNA expression in the fibroblasts or decreased ligand binding to the receptor. |
| T9 |
1294-1430 |
DRI_Approach |
denotes |
IFN-alpha and IFN-beta by themselves had little effect on promoter activity, but IFN-alpha augmented the inhibitory effect of IFN-gamma. |
| T10 |
1431-1569 |
DRI_Approach |
denotes |
Using a series of 5' deletion constructs, a proximal region of the COL1A1 promoter was shown to function as an IFN-gamma response element. |
| T11 |
1570-1745 |
DRI_Approach |
denotes |
This region of the gene harbors overlapping binding sites for transcription factors Sp1, Sp3, and NF-1 but no homologs of previously characterized IFN-gamma response elements. |
| T12 |
1746-1877 |
DRI_Outcome |
denotes |
The putative IFN-gamma response region was sufficient to confer inhibition of reporter gene expression by treatment with IFN-gamma. |
| T13 |
1878-2087 |
DRI_Background |
denotes |
Gel mobility shift analysis showed that two distinct and specific DNA-protein complexes were formed when fibroblast nuclear extracts were incubated with oligonucleotides spanning the IFN-gamma response region. |
| T14 |
2088-2168 |
DRI_Approach |
denotes |
IFN-gamma did not modify the ability of nuclear proteins to bind to this region. |
| T15 |
2169-2294 |
DRI_Outcome |
denotes |
The results indicate that IFN-gamma inhibits COL1A1 expression in fibroblasts principally at the level of gene transcription. |
| T16 |
2295-2432 |
DRI_Challenge |
denotes |
Inhibition involves IRF-1 and is mediated through a short proximal promoter segment but without an apparent change in promoter occupancy. |
| T17 |
2433-2534 |
DRI_Background |
denotes |
The findings provide novel insight into the mechanism of IFN-gamma regulation of fibroblast function. |