Serum amyloid P-component is an acute-phase reactant in the mouse

Pepys, Mark B.; Baltz, M L; Gomer, K. J.; Davies, A. J. S.; Doenhoff, Michael J.

doi:10.1038/278259a0

Cited by 266 publications

(145 citation statements)

References 11 publications

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“…47 To finally determine whether the effects of LXR ligands to suppress acute phase response gene expression are applicable in vivo, the synthetic LXR agonist T0901317 (20 mg/kg body weight per day) or vehicle (DMSO) was administered to C57Bl6/J and LXR␣␤ knockout mice 3 days before intraperitoneal LPS injection (3 mg/kg body weight). Twenty-four hours after LPS treatment animals were euthanized.…”

Section: Lxr Agonists Inhibit Acute Phase Response Gene Expression Inmentioning

confidence: 99%

A Nuclear Receptor Corepressor–Dependent Pathway Mediates Suppression of Cytokine-Induced C-Reactive Protein Gene Expression by Liver X Receptor

Blaschke

Takata

Caglayan

et al. 2006

Circulation Research

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Abstract-C-reactive protein (CRP), the prototypical human acute phase protein, is an independent risk predictor of future cardiovascular events, both in healthy individuals and in patients with known cardiovascular disease. In addition, previous studies indicate that CRP might have direct proatherogenic properties. Ligand activation of the liver X receptor (LXR), a member of the nuclear hormone receptor superfamily, inhibits inflammatory gene expression in macrophages and attenuates the development of atherosclerosis in various animal models. We demonstrate herein that 2 synthetic LXR ligands, T0901317 and GW3965, inhibit interleukin-1␤/interleukin-6 -induced CRP mRNA and protein expression in human hepatocytes. Knockdown of LXR␣/␤ by short interfering RNAs completely abolished the inhibitory effect of the LXR agonist T0901317 on cytokine-induced CRP gene transcription. Transient transfection experiments with 5Ј-deletion CRP promoter constructs identified a region from Ϫ125 to Ϫ256 relative to the initiation site that mediated the inhibitory effect of LXR ligands on CRP gene transcription. Depletion of the nuclear receptor corepressor by specific short interfering RNA increased cytokine-inducible CRP mRNA expression and promoter activity and reversed LXR ligand-mediated repression of CRP gene transcription. Chromatin immunoprecipitation assays indicated that nuclear receptor corepressor is present on the endogenous CRP promoter under basal conditions. Cytokine-induced clearance of nuclear receptor corepressor complexes was inhibited by LXR ligand treatment, maintaining the CRP gene in a repressed state. Finally, treatment of C57Bl6/J mice with LXR ligands attenuated lipopolysaccharide-induced mouse CRP and serum amyloid P component gene expression in the liver, whereas no effect was observed in LXR␣␤ knockout mice. Our observations identify a novel mechanism of inflammatory gene regulation by LXR ligands. Thus, inhibition of CRP expression by LXR agonists may provide a promising approach to impact initiation and progression of atherosclerosis. (Circ Res. 2006;99:e88-e99.)

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Section: Lxr Agonists Inhibit Acute Phase Response Gene Expression Inmentioning

confidence: 99%

A Nuclear Receptor Corepressor–Dependent Pathway Mediates Suppression of Cytokine-Induced C-Reactive Protein Gene Expression by Liver X Receptor

Blaschke

Takata

Caglayan

et al. 2006

Circulation Research

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“…In the mouse, SAP is a major acute-phase reactant (5). SAP is the precursor of tissue amyloid P component, where it may actually promote the formation of pathogenic amyloid deposits and prevent their degradation.…”

mentioning

confidence: 99%

Serum Amyloid P Component Binds to Fcγ Receptors and Opsonizes Particles for Phagocytosis

Bharadwaj

Mold

Markham

et al. 2001

The Journal of Immunology

149

150

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Serum amyloid P component (SAP) is a member of the pentraxin family of proteins. These proteins are characterized by cyclic pentameric structure, calcium-dependent ligand binding, and frequent regulation as acute-phase serum proteins. SAP is the serum precursor of the P component of amyloid. It binds to a broad group of molecules, including autoantigens, through a pattern recognition binding site. The related pentraxin, C-reactive protein (CRP), is a strong acute-phase reactant in man and an opsonin. We previously determined that the binding of CRP to leukocytes occurs through Fc receptors for IgG (FcγR). We now report that SAP also binds to FcγR and opsonizes particles for phagocytosis by human polymorphonuclear leukocytes (PMN). Specific, saturable binding of SAP to FcγRI, FcγRIIa, and FcγRIIIb expressed on transfected COS cells was detected using SAP-biotin and PE-streptavidin. Zymosan was used to test the functional consequences of SAP and CRP binding to FcγR. Both SAP and CRP bound to zymosan and enhanced its uptake by PMN. This enhanced phagocytosis was abrogated by treatment of PMN with wortmannin, a phosphatidylinositol-3 kinase inhibitor, or with piceatannol, a Syk inhibitor, consistent with uptake through FcγR. Treatment of PMN with phosphatidylinositol-specific phospholipase C to remove FcγRIIIb also decreased phagocytosis of SAP-opsonized zymosan, but not CRP-opsonized zymosan. These results suggest that SAP may function in host defense. In addition, as SAP binds to chromatin, a major immunogen in systemic lupus erythematosus, it may provide a clearance mechanism for this Ag through FcγR bearing cells.

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“…As reported in many studies, hSAP has a stable physiological concentration around 20-40 mg l À1 with an even higher C H P H C h C R P m S A P h S A P + C H P H C h S A P U N C H P H C h C R P m S A P h S A P + C H P H C h S A P U N C H P H C h C R P m S A P h S A P + C H P H C h S A P U N C H P H C h C R P m S A P h S A P + C H P H C h S A P U N DNA-binding affinity, 38 whereas mSAP is a major acute phase protein with widely differing concentration in different mouse strains. Although its value in all strains of mice rise greatly during the acute phase response, 39 the normal mice have a low concentration of SAP (around 5-10 mg l À1 in C57BL/6 mice and 40-60 mg l À1 in BALB/c mice), and their binding ability are much more weaker. 20,38 We therefore suggest that human beings may have developed the highly effective regulation of SAP expression, and the subsequent capability to prevent invasion of exogenous DNA, during the evolution of the innate immune system.…”

Section: Discussionmentioning

confidence: 99%

“…hSAP and mSAP was purified from human serum and mouse acute phase serum, respectively, as described earlier. 39,49 A chemical SAP inhibitor DHPHC was synthesized according to previous reports. 27 Plasmid pGL4.17-CMV was constructed by inserting a DNA fragment containing a CMV promoter into the multiple cloning site of pGL4.17 (Promega, Madison, WI, USA).…”

Section: Cell Culturementioning

confidence: 99%

Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine

et al. 2011

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The demonstration that naked plasmid DNA can induce strong immune responses in mice has attracted considerable attention in the vaccine community. However, similar immunizations have been less/not effective in clinical trials during the past decade, and the underlying mechanisms remain unknown. In this study, we hypothesized that some DNA-binding proteins in human serum may serve as host barriers, responsible for the low efficiency of plasmids' transfection in vivo. Using proteomics, we showed that human serum amyloid P component (hSAP) is specifically present in human DNA-protein complexes. Further analysis indicated that hSAP effectively binds plasmid DNA, inhibits DNA transfection into somatic cells and facilitates the endocytosis of DNA by macrophages, whereas mouse SAP (mSAP) has similar, but much weaker, activities. In the presence of hSAP, the plasmid DNA expression in vivo and plasmid DNA-induced immune responses also significantly decreased. Therefore, our results suggest that hSAP contributes to extracellular DNA clearance and the inhibition of plasmid DNA transfection in vivo. This mechanism may be partly responsible for the insufficient immune responses to DNA vaccination in human beings; therefore, it may serve as a novel target for the improvement of DNA vaccines and DNA-based gene therapy.

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Serum amyloid P-component is an acute-phase reactant in the mouse

Cited by 266 publications

References 11 publications

A Nuclear Receptor Corepressor–Dependent Pathway Mediates Suppression of Cytokine-Induced C-Reactive Protein Gene Expression by Liver X Receptor

A Nuclear Receptor Corepressor–Dependent Pathway Mediates Suppression of Cytokine-Induced C-Reactive Protein Gene Expression by Liver X Receptor

Serum Amyloid P Component Binds to Fcγ Receptors and Opsonizes Particles for Phagocytosis

Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine

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