Influence of endotoxin challenge on protein S and C4b‐binding protein in healthy subjects

Krabbe, K. S.; Bruunsgaard, Helle; Hillarp, Andreas; Thorsen, Sixtus

doi:10.1111/j.1538-7836.2005.01766.x

Cited by 1 publication

(1 citation statement)

References 18 publications

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“…Although Protein S would not appear to be an acute phase reactant, with protein levels having recently been shown to be largely unaffected by endotoxin challenge, interleukin 6 (IL6), a principle mediator of the acute phase response, has been shown to increase protein S mRNA levels in HepG2 cells (Hooper et al , 1995; Krabbe et al , 2006). It was concluded that this increase in mRNA level is due, at least in part to increased transcriptional activity, presumably mediated through interaction of the transcription factor NFIL6 (C/EBP β ) with the PROS1 promoter.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the human protein S gene promoter by liver enriched transcription factors

2006

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Summary Protein S is expressed in a number of tissue types, one of the most physiologically relevant being the liver. However, transcriptional control of protein S gene expression is poorly understood. We have characterised a 638 bp area in the 5′ flanking region of the human protein S gene, spanning all 10 previously reported transcription initiation sites, which demonstrates promoter activity in the human liver‐derived cell line HepG2. More refined reporter gene analysis of this region enabled the identification of three transcription initiation sites whose absence is associated with significantly reduced promoter activity, together with a number of positively and negatively acting transcriptional regulatory elements. Consistent with these findings, DNaseI footprinting analysis identified eleven sites (I–XI) from within this 638 bp region that show evidence of binding nuclear proteins. We present evidence to show that the liver‐specific factors hepatocyte nuclear factor 1 (HNF1) and HNF4 bind regions of the protein S promoter, which lie within the identified protein binding sites V and VIII, respectively, and that HNF4 activates the protein S promoter. Reporter gene analysis suggests that members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors are potent activators of protein S gene transcription in HepG2 cells.

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Section: Discussionmentioning

confidence: 99%