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The mouse C-reactive protein (CRP) gene is expressed in response to IL-1 but not IL-6
1Department of Microbiology, Ohio State University, Columbus 43210.
Abstract:
C-Reactive protein (CRP) is a minor acute phase reactant (APR) in the mouse, whereas CRP is the prototypical and one of the major positive APRs in all other mammals. MoCRP gene expression was tissue specific for the liver and induced by culture supernatants of LPS-activated macrophages. MoCRP gene expression by isolated hepatocytes in culture increased c, 3-fold in response to interleukin (IL)-1, but not IL-6. IL-6 is the most potent inflammatory cytokine for the induction of human CRP and many other APRs. By contrast, gene expression of the major APR of the mouse, serum amyloid P-component (SAP), a structural homologue of CRP, increased in response to either IL-1 or IL-6 under the same conditions. The region containing two potentially IL-1 responsive C/EBP elements in the moCRP gene failed to respond to IL-1 when a pCAT construct containing the elements was transfected into Hep 3B2 hepatoma cells. Therefore, IL-1 may influence the expression of the moCRP gene at the post-transcriptional rather than at the transcriptional level. The findings suggest that moCRP may be a minor APR because of the limited response of the gene to inflammatory cytokine signals.
Insights
Mouse C-Reactive protein (MoCRP) is a minor acute phase reactant (APR) due to limited cytokine response. Unlike in humans, interleukin-1, not interleukin-6, weakly induces MoCRP, suggesting post-transcriptional regulation.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- C-Reactive protein (CRP) is a major acute phase reactant (APR) in humans and most mammals.
- In mice, CRP (MoCRP) is considered a minor APR, with its regulation differing significantly from other species.
Purpose of the Study:
- To investigate the regulatory mechanisms of mouse C-Reactive protein (MoCRP) gene expression.
- To compare the induction of MoCRP by inflammatory cytokines with that of other mouse APRs.
Main Methods:
- Tissue-specific gene expression analysis of MoCRP.
- Hepatocyte culture and induction studies with interleukin-1 (IL-1) and interleukin-6 (IL-6).
- Reporter gene assays (pCAT constructs) to assess transcriptional regulation.
Main Results:
- MoCRP gene expression was primarily observed in the liver and induced by macrophage supernatants.
- IL-1, but not IL-6, weakly induced MoCRP expression in isolated hepatocytes (3-fold increase).
- Reporter gene assays indicated that IL-1 may affect MoCRP expression post-transcriptionally, not transcriptionally.
Conclusions:
- The limited response of the MoCRP gene to key inflammatory cytokines like IL-6 contributes to its status as a minor APR in mice.
- MoCRP regulation in mice differs from human CRP, highlighting species-specific inflammatory responses.
- Post-transcriptional mechanisms may play a significant role in controlling MoCRP levels.