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

2016 ◽  
Vol 473 (9) ◽  
pp. 1215-1224 ◽  
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.

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

2006 ◽  
Vol 136 (9) ◽  
pp. 2331-2337 ◽  
Author(s):  
Dietrich Rein ◽  
Elio Schijlen ◽  
Teake Kooistra ◽  
Karin Herbers ◽  
Lars Verschuren ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Wild Type ◽  
C Reactive Protein ◽  
Reactive Protein

scholarly journals Inhibition of Experimental Autoimmune Encephalomyelitis in Human C-Reactive Protein Transgenic Mice Is FcRIIB Dependent

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Xian-Zhen Hu ◽  
Tyler T. Wright ◽  
Nicholas R. Jones ◽  
Theresa N. Ramos ◽  
Gregory A. Skibinski ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Transgenic Mice ◽  
Fc Receptors ◽  
Subcutaneous Administration ◽  
Wild Type ◽  
C Reactive Protein ◽  
Autoimmune Encephalomyelitis ◽  
Similar Treatment ◽  
Reactive Protein ◽  
Experimental Autoimmune

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.

Expression of rabbit C-reactive protein in transgenic mice

1995 ◽  
Vol 73 (6) ◽  
pp. 521-531 ◽  
Author(s):  
CAROL S LIN ◽  
DONGYUAN XIA ◽  
JEUNG S YUN ◽  
THOMAS WAGNER ◽  
TERRY MAGNUSON ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
C Reactive Protein ◽  
Reactive Protein

Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins

Cell ◽  
1994 ◽  
Vol 76 (1) ◽  
pp. 117-129 ◽  
Author(s):  
David Westaway ◽  
Stephen J. DeArmond ◽  
Juliana Cayetano-Canlas ◽  
Darlene Groth ◽  
Dallas Foster ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Peripheral Nerves ◽  
Prion Proteins ◽  
Wild Type ◽  
The Central Nervous System

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

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

scholarly journals Borna Disease Virus Accelerates Inflammation and Disease Associated with Transgenic Expression of Interleukin-12 in the Central Nervous System

2002 ◽  
Vol 76 (23) ◽  
pp. 12223-12232 ◽  
Author(s):  
Susanna Freude ◽  
Jürgen Hausmann ◽  
Markus Hofer ◽  
Ngan Pham-Mitchell ◽  
Iain L. Campbell ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Disease Virus ◽  
Biologically Active ◽  
Interleukin 12 ◽  
Wild Type ◽  
Borna Disease Virus ◽  
The Central Nervous System ◽  
Borna Disease

ABSTRACT Targeted expression of biologically active interleukin-12 (IL-12) in astrocytes of the central nervous system (CNS) results in spontaneous neuroimmunological disease of aged mice. Borna disease virus (BDV) can readily multiply in the mouse CNS but does not trigger disease in most strains. Here we show that a large percentage of IL-12 transgenic mice developed severe ataxia within 5 to 10 weeks after infection with BDV. By contrast, no disease developed in mock-infected IL-12 transgenic and wild-type mice until 4 months of age. Neurological symptoms were rare in infected wild-type animals, and if they occurred, these were milder and appeared later. Histological analyses showed that the cerebellum of infected IL-12 transgenic mice, which is the brain region with strongest transgene expression, contained large numbers of CD4+ and CD8+ T cells as well as lower numbers of B cells, whereas other parts of the CNS showed only mild infiltration by lymphocytes. The cerebellum of diseased mice further showed severe astrogliosis, calcifications and signs of neurodegeneration. BDV antigen and nucleic acids were present in lower amounts in the inflamed cerebellum of infected transgenic mice than in the noninflamed cerebellum of infected wild-type littermates, suggesting that IL-12 or IL-12-induced cytokines exhibited antiviral activity. We propose that BDV infection accelerates the frequency by which immune cells such as lymphocytes and NK cells enter the CNS and then respond to IL-12 present in the local milieu causing disease. Our results illustrate that infection of the CNS with a virus that is benign in certain hosts can be harmful in such normally disease-resistant hosts if the tissue is unfavorably preconditioned by proinflammatory cytokines.

scholarly journals Human Factor H-Related Protein 5 Has Cofactor Activity, Inhibits C3 Convertase Activity, Binds Heparin and C-Reactive Protein, and Associates with Lipoprotein

2005 ◽  
Vol 174 (10) ◽  
pp. 6250-6256 ◽  
Author(s):  
Jennifer L. McRae ◽  
Thomas G. Duthy ◽  
Kim M. Griggs ◽  
Rebecca J. Ormsby ◽  
Peter J. Cowan ◽  
...  
Keyword(s):  
Human Factor ◽  
Factor H ◽  
Related Protein ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Cofactor Activity
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