Disease relevance of CRP

• The human CRP promoter is expressed in an inducible and cell-specific manner when linked to the bacterial CAT gene and transfected into human hepatoma cell cultures [1].
• The combined action of these cytokines causes fever, leukocytosis and the production of acute phase proteins such as C-reactive protein (CRP) [2].
• In protocol B, CRP, SAA, and IL-6 did not change in stable angina patients after angiography but increased in unstable angina patients (all P<0.05) [3].
• Weight loss was related with increased levels of the sTNF-Rs, sICAM-1, IL-6, LBP, and CRP [4].
• C-reactive protein (CRP) is a component of the acute phase response to infection, inflammation, and trauma [5].

Psychiatry related information on CRP

• Among others, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, serum amyloid A (SAA), and white blood cells (WBC) were measured, and dietary habits (including fish consumption) were evaluated using a validated food frequency questionnaire [6].
• Plasma concentrations of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), C reactive protein (CRP) and alpha-1-antichymotrypsin (ACT) in 145 patients with probable Alzheimer's disease (AD) and 51 non-demented controls were measured [7].
• After adjustment for age, race, smoking status, history of diabetes, history of cardiovascular disease, physical activity, high-density lipoprotein cholesterol, antiinflammatory medications, statins, and total fat mass, alcohol intake showed a J-shaped relationship with mean IL-6 (P for quadratic term <0.001) and CRP (P=0.014) levels [8].
• Strategies for decreasing elevated CRP include administration of statins, thiazolidinediones, and metformin; moderate alcohol consumption and appropriate weight loss are also helpful in this regard [9].
• Risk reduction strategies designed to lower plasma CRP may be effective by improving NO bioavailability [10].

High impact information on CRP

• In matched analyses, the odds ratio (OR) for incident CHD in the highest vs lowest quartile was 2.3 for CRP (95% confidence interval [CI], 1.4-3.7; P for trend =.002) and 3.3 for IL-6 (95% CI, 2.0-5.5; P for trend <.001) [11].
• Ethnic groups show differences in levels of visceral adiposity, insulin resistance, and novel risk markers such as C-reactive protein (CRP), adiponectin and plasma homocysteine [12].
• Furthermore, stimulation of neutrophils with CRP or with peptides 174-185 or 201-206 promoted a loss of membrane-bound IL-6R, suggesting release by proteolytic shedding [13].
• However, this interaction could not account for the majority of binding of CRP to neutrophils or monocytic cells [14].
• C-reactive protein (CRP) is an acute phase serum protein that shares several functions with immunoglobulin (Ig)G including complement activation and binding to receptors on monocytes and neutrophils [14].

Chemical compound and disease context of CRP

• C-reactive protein (CRP), the major human acute-phase plasma protein, binds to phosphocholine (PCh) residues present in pneumococcal C-polysaccharide (PnC) of Streptococcus pneumoniae and to PCh exposed on damaged and apoptotic cells [15].
• RESULTS: The index patient's disease was refractory to treatment with prednisone (30 mg/day) and MTX, with spiking fevers, rash, synovitis, a serum ferritin level of 8,400 ng/ml (normal </=200), and a CRP level of 86 mg/liter (normal <8) [16].
• METHODS: Plasmas (EDTA) as well as clinical data, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected in two groups of 10 patients fulfilling the European Spondylarthropathy Study Group criteria for SpA or the 1987 American College of Rheumatology criteria for RA [17].
• SUBJECTS AND METHODS: We investigated the cross-sectional and longitudinal association of adiponectin with CRP and IL-6 in 41 morbidly obese women with different stages of glucose tolerance before and 17 months after significant weight loss induced by gastric surgery [18].
• C-reactive protein (CRP) and neopterin were measured in 22 patients with acute coronary syndromes, 50 patients with stable vascular disease and 22 healthy controls [19].

Biological context of CRP

• IL-6 is a pleiotropic cytokine acting on several cell lineages, and, at the hepatocyte level, stimulates the synthesis of acute phase proteins, such as the well known C-Reactive Protein (CRP) [20].
• The data were compared with conventional parameters of inflammation, such as C-reactive protein (CRP), iron and hemoglobin levels, erythrocyte sedimentation rate (ESR), white blood cell (WBC) counts, and platelet counts [21].
• Adiponectin plasma levels and adipose-tissue gene expression were significantly lower in obese subjects and inversely correlated with obesity-associated variables, including high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6) [22].
• These results further identify amino acids involved in the binding sites on CRP for FcgammaRI, FcgammaRIIa, and C1q and indicate that these sites are overlapping [23].
• CRP binds to microbial antigens and damaged cells, opsonizes particles for phagocytosis and regulates the inflammatory response by the induction of cytokine synthesis [23].

Anatomical context of CRP

• The pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP) are acute-phase proteins produced by liver epithelial cells [24].
• The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and the level of several cytokines in serum and synovial fluid were also determined [25].
• Incubation of Hep 3B cells with conditioned medium from LPS-stimulated monocytes, in the absence of dexamethasone, led to modest induction of SAA or CRP, but addition of dexamethasone potentiated this response in a dose-dependent manner [26].
• Because several proatherogenic effects of CRP have been documented in endothelial cells, we examined human aortic endothelial cells (HAEC) for CRP production [27].
• These results suggest that CRP can alter the cytokine profile of mouse macrophages by acting through FcgammaR leading to a down-regulation of the inflammatory response [5].

Associations of CRP with chemical compounds

• Cooperativity is maintained when the CRP promoter is linked to a different coding region, that of the bacterial neomycin phosphotransferase II gene [1].
• Plasma tumor necrosis factor (TNF) and IL-1 beta levels were unaffected, whereas serum C-reactive protein (CRP) concentrations increased slightly and plasma IL-1 receptor antagonist (IL-1RA) levels increased markedly [28].
• White blood cells (WBCs), C-reactive protein (CRP) levels and/or erythrocyte sedimentation rate, and ferritin levels were measured and, in 1 patient, serum creatinine levels were determined [16].
• Complement was required for the protective effect of CRP as cobra venom factor treatment eliminated the effect of CRP in both gamma-chain-deficient and wild-type mice, and CRP failed to protect C3- or C4-deficient mice from infection [29].
• CRP and anti-PC Ab share the ability to bind to PC on the cell wall C-polysaccharide of S. pneumoniae and to activate complement [29].

Physical interactions of CRP

• Using the surface plasmon resonance technique and a panel of recombinantly expressed FH constructs, we observed that CRP binds to two closely located regions on short consensus repeat (SCR) domains 7 and 8-11 of FH [30].
• Binding of CRP to oxidized LDL did not interfere with binding of annexin A5, and vice versa [31].
• Basal CRP expression increased dramatically when binding of both OCT-1 and NF-kappaB was abolished [32].
• In contrast, all five CRP mutants bound to Fn as well as did wild-type CRP [15].
• By contrast, the 360 bp promoter of the CRP gene was bound only by STAT3 at consensus sites at -93, -142, -173, and -287 from the start site; however, a single consensus site for C/EBP at -75 was not recognized [33].

Regulatory relationships of CRP

• In hepatoma Hep3B cells, IL-6 induces CRP expression by activating transcription factors STAT3 and C/EBPbeta [32].
• While previous studies have indicated that IL-6 induces transcription of CRP, the mode of action of IL-1 has not been clearly defined [34].
• CRP production was significantly inhibited by the p38 MAPK specific inhibitor RWJ 67657 at 1 micromol/l, which is pharmacologically relevant [35].
• However, the addition of the RGDS and RGDSPASSLP cell-binding peptides of Fn to cells enhanced attachment to the active peptide from CRP [36].
• Our findings suggest that in healthy people, basal CRP levels are regulated by IL1B but not by IL6 genetics [37].

Other interactions of CRP

• IFN-gamma increases were also abrupt, preceding those of fever and CRP by one day [38].
• TNF alpha and C-reactive protein (CRP) levels were below the detection limit in the same plasma samples [39].
• Thus, PTX3, unlike the classical pentraxins CRP and SAP, is expressed and released by cells of the monocyte-macrophage lineage exposed to inflammatory signals [24].
• Ca2+ did not inhibit binding of CRP to Fn at pH 6.5 and lower [40].
• Transforming growth factor-beta (TGF-beta) modified production of the major human acute phase reactant, C-reactive protein (CRP), induced by the inflammatory cytokines, IL-1 beta or IL-6 [41].

Analytical, diagnostic and therapeutic context of CRP

• C-reactive protein (CRP) was assayed by radial immunodiffusion [38].
• No significant difference was observed in CRP, cytokine, and hydrolase plasma levels after ERCP [42].
• Baseline CRP and SAA levels correlated with their peak values after PTCA and angiography (all P<0.001) [3].
• We detected the presence of CRP mRNA by RT-PCR and in situ hybridization, intracellular protein by Western blot and secreted protein by ELISA [27].
• We used site-directed mutagenesis to analyze the contribution of Phe(66) and Glu(81) to the binding of CRP to PCh, and to generate a CRP mutant that does not bind to PCh-containing ligands [15].

References