Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Background/aims: Liver injury results in the activation of hepatic stellate cells (HSCs), which in turn produce matrix metalloproteinase (MMP) in response to pro-inflammatory cytokines for tissue remodelling. This study explored the transcriptional induction of the MMP-1 gene by tumour necrosis factor-alpha (TNF-alpha) in HSCs.
Methods: The LI90 human HSC line was used in the present study. Gelatin zymography, enzyme-linked immunosorbent assay, Northern blotting and gene promoter-reporter assays were used to analyse the induction of MMP-1 protein, mRNA expression and gene transcription respectively. Deletional or site-directed mutations were introduced into the promoter region and transiently transfected into LI90 cells to determine the cis-acting elements necessary for TNF-alpha inducibility. Gel shift mobility assays were used to determine the transcriptional factors involved in the TNF-alpha responsiveness.
Results: TNF-alpha upregulated MMP-1 protein and mRNA expression in a dose-dependent manner. A time-course experiment revealed a rapid induction of MMP-1 mRNA expression after TNF-alpha treatment. Mutation in a putative nuclear factor (NF)-kappaB-binding site at -2541 bp almost completely abolished the TNF-alpha response to MMP-1 gene-promoter activity, suggesting transcriptional regulation of MMP-1 expression by TNF-alpha via this site. Electrophoretic mobility shift assay and supershift assays indicated that this transcriptional regulation was regulated via the p50/p50 homodimer of NF-kappaB.
Conclusions: MMP-1 gene expression might be induced by TNF-alpha via the p50/p50 homodimer of NF-kappaB in activated human HSCs.
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Source |
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http://dx.doi.org/10.1111/j.1478-3231.2008.01883.x | DOI Listing |
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