Interleukin-6-dependent and -independent regulation of the human C-reactive protein gene

We have investigated the function of different mediators of the regulation of the human C-reactive protein (hCRP) gene in transgenic mice. hCRP was induced by lipopolysaccharide and wounding in interleukin-6 (IL-6) +/+ mice, but not in IL-6 -/- mice. This finding suggested that IL-6 is necessary for the induction of hCRP. However, injection of IL-6 did not induce the hCRP gene. Thus, the induction of hCRP by IL-6 seems to require an additional cofactor. Therefore, we screened different cytokines for their activity in IL-6 +/+ and IL-6 -/- mice. Surprisingly, interleukin-1β, as well as oncostatin M or leukaemia inhibitory factor, led to an induction of hCRP in both genetic backgrounds. These results indicate an IL-6-dependent and -independent regulation of hCRP. These hCRP transgenic mice therefore represent a novel model system for defining the cytokine network involved in the regulation of acute-phase genes during the course of inflammation.

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Increased expression of C-reactive protein gene in inflamed gingival tissues could be derived from endothelial cells stimulated with interleukin-6

Archives of Oral Biology ◽

10.1016/j.archoralbio.2011.04.010 ◽

2011 ◽

Vol 56 (11) ◽

pp. 1312-1318 ◽

Cited By ~ 13

Author(s):

Tomoki Maekawa ◽

Koichi Tabeta ◽

Keiko Kajita-Okui ◽

Takako Nakajima ◽

Kazuhisa Yamazaki

Keyword(s):

Endothelial Cells ◽

Interleukin 6 ◽

Protein Gene ◽

C Reactive Protein ◽

Reactive Protein

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STAT3 Participates in Transcriptional Activation of the C-reactive Protein Gene by Interleukin-6

Journal of Biological Chemistry ◽

10.1074/jbc.271.16.9503 ◽

1996 ◽

Vol 271 (16) ◽

pp. 9503-9509 ◽

Cited By ~ 171

Author(s):

Dongxiao Zhang ◽

Ming Sun ◽

David Samols ◽

Irving Kushner

Keyword(s):

Transcriptional Activation ◽

Interleukin 6 ◽

Protein Gene ◽

C Reactive Protein ◽

Reactive Protein

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Regulation of the Human C-reactive Protein Gene in Transgenic Mice

Journal of Biological Chemistry ◽

10.1074/jbc.270.2.704 ◽

1995 ◽

Vol 270 (2) ◽

pp. 704-708 ◽

Cited By ~ 32

Author(s):

Carol Murphy ◽

Johannes Beckers ◽

Ulrich Rüther

Keyword(s):

Transgenic Mice ◽

Protein Gene ◽

C Reactive Protein ◽

Reactive Protein

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Interleukin-6 is necessary, but not sufficient, for induction of the humanC-reactive protein gene in vivo

Biochemical Journal ◽

10.1042/bj3250617 ◽

1997 ◽

Vol 325 (3) ◽

pp. 617-621 ◽

Cited By ~ 49

Author(s):

Birgit WEINHOLD ◽

Augustinus BADER ◽

Valeria POLI ◽

Ulrich RÜTHER

Keyword(s):

Transgenic Mice ◽

Acute Phase ◽

Interleukin 6 ◽

Acute Phase Reactant ◽

Primary Hepatocytes ◽

Cytokine Network ◽

Gene Encoding ◽

Reactive Protein

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.

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