Transgenic Flavonoid Tomato Intake Reduces C-Reactive Protein in Human C-Reactive Protein Transgenic Mice More Than Wild-Type Tomato

We showed earlier that experimental autoimmune encephalomyelitis (EAE) in human C-reactive protein (CRP) transgenic mice (CRPtg) has delayed onset and reduced severity compared to wild-type mice. Since human CRP is known to engage Fc receptors and Fc receptors are known to play a role in EAE in the mouse, we sought to determine if FcRI, FcRIIb, or FcRIII was needed to manifest human CRP-mediated protection of CRPtg. We report here that in CRPtg lacking either of the two activating receptors, FcRI and FcRIII, the beneficial effects of human CRP are still observed. In contrast, if CRPtg lack expression of the inhibitory receptor FcRIIB, then the beneficial effect of human CRP is abrogated. Also, subcutaneous administration of purified human CRP stalled progression of ongoing EAE in wild-type mice, but similar treatment failed to impede EAE progression in mice lacking FcRIIB. The results reveal that a axis is responsible for protection against EAE in the CRPtg model.

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Human C-reactive protein impedes entry of leptin into the CNS and attenuates its physiological actions in the CNS

Biochemical Journal ◽

10.1042/bj20151282 ◽

2016 ◽

Vol 473 (9) ◽

pp. 1215-1224 ◽

Cited By ~ 3

Author(s):

Jie Li ◽

Dong Wei ◽

Mark A. McCrory ◽

Alexander J. Szalai ◽

Gangyi Yang ◽

...

Keyword(s):

Central Nervous System ◽

Transgenic Mice ◽

Negative Impact ◽

Leptin Resistance ◽

Related Protein ◽

Wild Type ◽

C Reactive Protein ◽

Reactive Protein ◽

Fluid Concentration ◽

Agouti Related Protein

Defective central leptin signalling and impaired leptin entry into the CNS (central nervous system) represent two important aspects of leptin resistance in obesity. In the present study, we tested whether circulating human CRP (C-reactive protein) not only diminishes signalling of leptin within the CNS, but also impedes this adipokine's access to the CNS. Peripheral infusion of human CRP together with co-infused human leptin was associated with significantly decreased leptin content in the CSF of ob/ob mice. Furthermore, following peripheral infusion of human leptin, the CSF (cerebrospinal fluid) concentration of leptin in transgenic mice overexpressing human CRP was sharply lower than that achieved in similarly infused wild-type mice. Administration of LPS (lipopolysaccharide) to human CRP-transgenic mice dramatically elevated the concentrations of human CRP in the CSF. The i.c.v. (intracerebroventricular) delivery of human CRP into the lateral ventricles of ob/ob mice blocked the satiety and weight-reducing actions of human leptin, but not those of mouse leptin. I.c.v. injection of human CRP abolished hypothalamic signalling by human leptin, and ameliorated the effects of leptin on the expression of NPY (neuropeptide Y), AgRP (Agouti-related protein), POMC (pro-opiomelanocortin) and SOCS-3 (suppressor of cytokine signalling 3). Human CRP can impede the access of leptin to the CNS, and elevation of human CRP within the CNS can have a negative impact on the physiological actions of leptin.

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W01.43 Evidence for anti-inflammatory activity of statins and fibrates from studies in human C-reactive protein transgenic mice and in cultured human hepatocytes

Atherosclerosis ◽

10.1016/s0021-9150(04)90043-3 ◽

2004 ◽

Vol 5 (1) ◽

pp. 10

Author(s):

R KLEEMANN

Keyword(s):

Transgenic Mice ◽

Human Hepatocytes ◽

Inflammatory Activity ◽

C Reactive Protein ◽

Reactive Protein ◽

Anti Inflammatory

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Expression of rabbit C-reactive protein in transgenic mice

Immunology and Cell Biology ◽

10.1038/icb.1995.82 ◽

1995 ◽

Vol 73 (6) ◽

pp. 521-531 ◽

Cited By ~ 22

Author(s):

CAROL S LIN ◽

DONGYUAN XIA ◽

JEUNG S YUN ◽

THOMAS WAGNER ◽

TERRY MAGNUSON ◽

...

Keyword(s):

Transgenic Mice ◽

C Reactive Protein ◽

Reactive Protein

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W01.43 Evidence for anti-inflammatory activity of statins and fibrates from studies in human C-reactive protein transgenic mice and in cultured human hepatocytes

Atherosclerosis Supplements ◽

10.1016/s1567-5688(04)90043-3 ◽

2004 ◽

Vol 5 (1) ◽

pp. 10

Author(s):

R. Kleemann ◽

L. Verschuren ◽

B. de Rooij ◽

J. Lindeman ◽

A. Szalai ◽

...

Keyword(s):

Transgenic Mice ◽

Human Hepatocytes ◽

Inflammatory Activity ◽

C Reactive Protein ◽

Reactive Protein ◽

Anti Inflammatory

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4P-1178 Direct in vivo down-regulation of IL-1-induced C-reactive protein (CRP) expression by statins and fibrates in human CRP transgenic mice

Atherosclerosis Supplements ◽

10.1016/s1567-5688(03)91434-6 ◽

2003 ◽

Vol 4 (2) ◽

pp. 334

Author(s):

H. Princen ◽

B.-J. De Rooij ◽

A.J. Szalai ◽

M. De Maat ◽

T. Kooistra ◽

...

Keyword(s):

Transgenic Mice ◽

C Reactive Protein ◽

Down Regulation ◽

Reactive Protein

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Attenuation of complement-mediated acute lung injury in rabbits and transgenic mice by C-reactive protein

CHEST Journal ◽

10.1378/chest.105.3.101s ◽

1994 ◽

Vol 105 (3) ◽

pp. 101S-101 ◽

Cited By ~ 1

Author(s):

R. O. Webster ◽

R. Heuertz ◽

D. Xia ◽

D. Samols

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Transgenic Mice ◽

C Reactive Protein ◽

Reactive Protein

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Tolerance and immunity to the inducible self antigen C-reactive protein in transgenic mice

European Journal of Immunology ◽

10.1002/eji.1830251242 ◽

1995 ◽

Vol 25 (12) ◽

pp. 3489-3495 ◽

Cited By ~ 15

Author(s):

Thomas C. Klein ◽

Rainer Döffinger ◽

Mark B. Pepys ◽

Ulrich Rüther ◽

Bruno Kyewski

Keyword(s):

Transgenic Mice ◽

C Reactive Protein ◽

Reactive Protein ◽

Self Antigen

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Hepatic but Not CNS-Expressed Human C-Reactive Protein Inhibits Experimental Autoimmune Encephalomyelitis in Transgenic Mice

Autoimmune Diseases ◽

10.1155/2015/640171 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Tyler T Wright ◽

Rachel V. Jimenez ◽

Todd E. Morgan ◽

Namrata Bali ◽

Xiaogang Hou ◽

...

Keyword(s):

Experimental Autoimmune Encephalomyelitis ◽

Transgenic Mice ◽

Gene Promoter ◽

C Reactive Protein ◽

Autoimmune Encephalomyelitis ◽

Reactive Protein ◽

Protective Actions ◽

Dependent Protein ◽

Low Levels ◽

Experimental Autoimmune

We recently demonstrated that human C-reactive protein (CRP), expressed hepatically in transgenic mice (CRPtg), improved the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The liver is the primary site of CRP synthesis in humans and in CRPtg mice but is also expressed by both at low levels in the CNS. To determine if CNS expression of human CRP is sufficient to impact EAE, we generated neuronal CRP transgenic mice (nCRPtg) wherein human CRP expression is driven by the neuron-specific Ca2+/calmodulin-dependent protein kinase IIα(CaMKIIα) gene promoter. We found that hepatically expressed/blood-borne CRP, but not CNS expressed CRP, lessened EAE severity. These outcomes indicate that the protective actions of human CRP in EAE are manifested in the periphery and not in the CNS and reveal a previously unappreciated site specificity for the beneficial actions of CRP in CNS disease.

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