Interleukin-6 is necessary, but not sufficient, for induction of the humanC-reactive protein gene in vivo.
We have investigated the involvement of interleukin-6 (IL-6) in the induction of the gene encoding the acute-phase protein human C-reactive protein (hCRP). In transgenic mice the hCRP gene can be induced by lipopolysaccharide (LPS), but not by IL-6. In contrast, hCRP was inducible by IL-6 in primary human hepatocytes and in primary hepatocytes isolated from transgenic mice. To further evaluate the role of IL-6, we introduced the hCRP transgene into animals lacking endogenous IL-6 (IL-6-negative mice). Here, hCRP was not inducible by LPS, but was induced by a combination of LPS and IL-6. These results clearly demonstrate that IL-6 is necessary, but not sufficient, for the induction of hCRP expression. These animal models will allow further dissection of the cytokine network responsible for the regulation of the major human acute-phase reactant CRP.
Weinhold
B
B
Institut für Molekularbiologie, Medizinische Hochschule Hannover OE 5250, 30623 Hannover, Germany.
Bader
A
A
Poli
V
V
Rüther
U
U
D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic
D015850:Interleukin-6; D008070:Lipopolysaccharides; D002097:C-Reactive Protein