C-reactive Protein Protein Research Articles

Maternal c-reactive protein and oxidative stress markers as predictors of delivery latency in patients experiencing preterm premature rupture of membranes.

To evaluate the usefulness of maternal serum c-reactive protein (CRP), lipid peroxide, and oxygen radical absorbance capacity (ORAC), to predict the interval between membrane rupture and delivery in patients with preterm premature rupture of membranes (PPROM). The present prospective study included patients with singleton pregnancies experiencing PPROM at earlier than 34weeks of pregnancy who underwent spontaneous vaginal delivery between August 1, 2010 and July 31, 2013 at Chonnam National University Hospital, Republic of Korea. Patients were categorized based on whether delivery occurred within 3days of PPROM or after. CRP levels, lipid peroxide (using malondialdehyde levels), ORAC, protein carbonyl, and other potential risk factors were compared between the groups. There were 72 patients included. Maternal serum CRP levels, malondialdehyde levels, and Bishop Score were higher in patients who underwent delivery within 3days (all P<0.05); ORAC levels were lower among these patients (P=0.002). A receiver operating characteristic curve analysis showed that CRP, malondialdehyde, and ORAC levels were predictive of delivery within 3days after PPROM. Maternal serum CRP, malondialdehyde, and ORAC levels at admission were useful in predicting the latent period in patients with PPROM.

Preliminary indications of the effect of a brief yoga intervention on markers of inflammation and DNA methylation in chronically stressed women

Yoga is associated with reduced stress and increased well-being, although the molecular basis for these benefits is not clear. Mounting evidence implicates the immune response, with current studies focused on protein immune markers (such as cytokines) in clinical populations. To explore the molecular impact, this pilot study uses a subsample (n=28) from a randomised waitlist control trial investigating the impact of an 8-week yoga intervention in a community population of women reporting psychological distress (N=116). We measured interleukin-6 (IL-6), tumour necrosis factor (TNF) and C-reactive protein (CRP) protein levels, and the DNA methylation of these genes and the global indicator, LINE-1. Correlations between these and psychological variables were explored, identifying moderate correlations with CRP protein levels, and methylation of IL-6, CRP and LINE-1. Many cytokine samples were below detection, however a Mann–Whitney U demonstrated a trend of moderate between-group effect for elevated IL-6 in the yoga group. Methylation analyses applied cross-sectional and non-controlled longitudinal analyses. Waist-to-height ratio and age were covaried. We demonstrated reduced methylation of the TNF region in the yoga group relative to the waitlist control group. No other genes demonstrated a significant difference. Longitudinal analysis further supported these results. This study is one of the first to explore yoga and immunological markers in a non-clinical population, and is the first study to explore DNA methylation. These findings indicate that further research into molecular impact of yoga on markers of immune function is warranted, with larger studies required.

Systemic inflammation and painful joint burden in osteoarthritis: a matter of sex?

We investigated the association between serum levels of C-reactive protein (CRP) and the extent of multijoint pain among individuals with hip/knee osteoarthritis (OA) and determined whether the association differs by sex. Serum CRP and cartilage oligomeric matrix protein (COMP) were determined by enzyme-linked immunosorbent assay (ELISA) in 189 individuals (101 female, 88 male) scheduled for total hip/knee arthroplasty for OA. Patients indicated on a homunculus all painful joints; a summed count was derived. A series of negative binomial regression models was used to investigate the cross-sectional association between painful joint count (outcome) and serum CRP concentrations, adjusting for age, sex, body mass index (BMI), comorbidity count and COMP. An interaction between sex and these biomarkers was tested. Mean age: 66 among women, 65 among men. Women had higher mean joint count (3.7 vs 2.5, P<0.01; 4+joint count reported by 37% women, 25% men). Median CRP concentration was higher in women (15.4mg/l vs 9.3, P=0.07). From adjusted analyses, the effects of both ln(CRP) and ln(COMP) were modified by sex (P<0.05). Increasing ln(CRP) was associated with greater painful joint count among women, but not men. There may be a dose-response association between painful joint burden in OA and systemic inflammation, and it appears the association is sex-specific, which may in part explain inconsistent findings in the literature. Our results underline the importance of showing sex-specific associations in OA, especially when studying the influence of inflammation.

Occupational exposure levels of bioaerosol components are associated with serum levels of the acute phase protein Serum Amyloid A in greenhouse workers.

BackgroundOccupational exposure to particles may be associated with increased inflammation of the airways. Animal experiments suggest that inhaled particles also induce a pulmonary acute phase response, leading to systemic circulation of acute phase proteins. Greenhouse workers are exposed to elevated levels of bioaerosols. The objective of this study is to assess whether greenhouse workers personal exposure to bioaerosol components was associated with serum levels of the acute phase proteins Serum Amyloid A (SAA) and C-reactive protein (CRP).MethodsSAA and CRP levels were determined in serum sampled repeatedly from 33 greenhouse workers. Blood was drawn repeatedly on Mondays and Thursdays during work weeks. Acute phase protein levels were compared to levels in a comparison group of 42 people and related to individual exposure levels to endotoxin, dust, bacteria, fungi and β-glucan.ResultsSerum levels of SAA and CRP were not significantly different in greenhouse workers and a reference group, or on the two work days. In a mixed model, SAA levels were positively associated with endotoxin exposure levels (p = 0.0007). Results for fungi were not clear. CRP levels were positively associated with endotoxin exposures (p = 0.022). Furthermore, when workers were categorized into three groups based on SAA and CRP serum levels endotoxin exposure was highest in the group with the highest SAA levels and in the group with middle and highest CRP levels. SAA and CRP levels were elevated in workers with asthma.ConclusionGreenhouse workers did not have elevated serum levels of SAA and CRP compared to a reference group. However, occupational exposure to endotoxin was positively associated with serum levels of the acute phase proteins SAA and CRP. Preventive measures to reduce endotoxin exposure may be beneficial.

Mechanism and Clinical Significance of IL-6 Combined with TNF-α or IL-1 for the Induction of Acute Phase Proteins SAA and CRP in Chronic Inflammatory Diseases

Serum amyloid A (SAA) and C-reactive protein (CRP) are two major acute phase proteins whose serum concentrations increase in response to inflammation, though the exact mechanism underlying this induction remains unknown. Dysregulated production of interleukin (IL)-6 plays a pathogenic role in various inflammatory diseases such as rheumatoid arthritis, Castleman’s disease and systemic juvenile idiopathic arthritis. IL-6 blocking therapy with an anti-IL-6 receptor antibody (tocilizumab) can ameliorate clinical symptoms and abnormal laboratory findings, and completely normalize CRP and SAA levels in rheumatoid arthritis patients. Conversely, therapy for blocking tumor necrosis factor (TNF)-α, another key pathogenic factor in rheumatoid arthritis, barely lowers CRP and SAA to within their normal range, suggesting that IL-6 and TNF-α play different roles in the induction of acute phase protein expression. To clarify the different pathogenic roles and mechanisms of IL-6 and TNF-α or IL-1 in the induction of CRP and SAA in chronic inflammatory diseases, we investigated the transcriptional regulation mechanisms of SAA and CRP using hepatoma-derived cell lines in vitro, and related these mechanisms to the different effects of IL-6 and TNF-α blocking therapies on serum SAA and CRP in rheumatoid arthritis patients in vivo. We propose transcriptional regulation models for inflammatory cytokine-induced SAA and CRP expression that explain why IL-6 plays an essential role in the induction of SAA and CRP in the presence of inflammation.

C-Reactive Protein –Biological Marker of Inflammation in Patients with Pneumonia

Abstract Introduction. The term biomarkers or biological markers generally refers to proteins measured in the circulation (blood), whose concentration indicates some normal or pathological state or condition. The biomarker is objectively measured and evaluated as an indicator of normal biological processes or pharmacological responses to therapeutic interventions. One of these biological markers is C-reactive protein (CRP). Aim. To evaluate the efficiency of using adequate and appropriate biomarkers for diagnosis, treatment and monitoring of pneumonia in children. Methods. This study included 30 patients with diagnosed pneumonia, who were admitted at our Institute. Blood samples were taken prior to initiation of treatment in patients with pneumonia and 7 and 14 days after the treatment. The control group included physically active and healthy individuals without family history of disease, aged from 1 to 14 years. All the results of the biochemical analyses were within the reference values, and none of the control individuals received therapy. In our country, for serum C-reactive protein, as well as for other parameters that determine the diagnosis of the patient, we use a common method for determining normal values, by choosing a huge representative sample from the screening population, consisting of healthy individuals without any disease, especially with no sign of this disease (the children who should be checked up). Further, normal values obtained in this way are taken as reference values. Results. The average serum CRP protein levels prior to antibiotic therapy were the following: (1-2) x̄±sd =34.94±20.44 mg/L, (3-6) x̄±sd=68.20±10.87 mg/L, (7-11) x̄±sd=65.59±12.01 mg/L, whereas in patients with pneumonia after 7-day antibiotic treatment the values were the following: x̄±sd=24.64 ± 11.57 mg/L/x̄±sd =40.10±6.83 mg/L/x̄±sd=32.09±6.68 mg/L (P&lt;0.05), and after 14-day-therapy x̄±sd=6.80±1.14 mg/L/x̄± sd=7.20±0.82 mg/L/x̄±sd=8.10±0.89 mg/L (P&lt;0.05). Also, CRP in serum correlated with the severity of the clinical condition (P&lt;0.05). Discussion and conclusion. This study is useful for showing the importance of C-reactive protein in serum for early diagnosis and follow-up of the pneumonia. CRP is very important as a biomarker, both from clinical and scientific aspect. It can be used for early rapid diagnosis, monitoring of pneumonia and can successfully be used in a large number of diagnosis. It opens new opportunities for further research in this field.

Serum C-reactive protein and C-reactive gene (-717C&gt;T) polymorphism are not associated with periodontitis in Indonesian male patients

Background: Periodontitis is an inflammatory disease caused by periodontal pathogens and influenced by multiple risk factors such as genetics, smoking habit, age and systemic diseases. The inflammatory cascade is characterized by the release of C-reactive protein (CRP). Periodontitis has been reported to have plausible links to increased level of CRP, which in turn has been associated to elevated risk of cardiovascular disease (CVD). Purpose: The purpose of this study was t o investigate the relationship amongst the severity of periodontitis, CRP level in blood and CRP (-717 C>T) gene polymorphism in male Indonesian smokers and non-smokers. Method: The severity of periodontitis was assessed for 97 consenting male Indonesian smokers and non-smokers. The CRP level of the subjects was determined by using immuno-turbidimetric assay performed in PARAHITA Diagnostic Center Laboratory ISO 9001: 2000 Cert No. 15225/2. The rate of CRP (-717C>T) gene polymorphism was determined by using PCR-RFLP in Oral Biology Laboratory, Faculty of Dentistry, Universitas Indonesia. Result: The results suggest that the CRP protein level is not significantly associated with the tested CRP gene polymorphism (p>0.05). Also, while the severity of periodontitis increased significantly with subject age, the CRP level in blood serum was not significantly related to the severity of periodontitis. The genotypes of the tested polymorphism did not show significant association with the severity of periodontitis either in smokers or in the combined population including smokers and non-smokers. The results naturally do not exclude such associations, but suggest that to discern the differences the sample size must be considerably increased. Conclusion: The CRP (-717C>T) gene polymorphism and CRP level in blood serum were not found to be associated with the severity of periodontitis in male smokers or in the combined population of smokers and non-smokers.

Upregulation of circulating cytokeratin 20, urokinase plasminogen activator and C-reactive protein is associated with poor prognosis in gastric cancer.

Gastric cancer is one of the most common types of cancer, with a high mortality rate. The aim of this study was to investigate the role of several key molecules, including cytokeratin (CK) 19 and CK20, urokinase plasminogen activator (uPA), C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9, which are involved in cancer invasion and metastasis, in order to determine whether they may be considered as novel prognostic factors for gastric cancer. Peripheral blood was collected from 165 patients with gastric adenocarcinoma who underwent curative surgical resection at Zhejiang Cancer Hospital (Hangzhou, China) between 2010 and 2011. The mRNA levels of CK19, CK20, uPA and MMP-9 were detected by reverse transcription-quantitative polymerase chain reaction. The protein expression of CRP was measured by immunoturbidimetry. The Students t-test was used in the univariate analyses and the Kaplan-Meier method was used to analyze the survival curves. The relative mRNA expression of CK19 and MMP-9 was not found to be significantly associated with gender, age or cancer stage, whereas that of CK20 and uPA was associated with gastric cancer stage: The low-expression group was associated with early-stage and the high-expression group with more advanced-stage disease (P<0.05). The CRP protein level was associated with gender and cancer stage: The low-expression group was predominantly associated with male gender and early-stage disease, whereas the high-expression group was associated with female gender and advanced-stage disease (P<0.05). The expression of CK19, CK20, uPA and CRP, but not MMP-9, was negatively associated with overall survival (OS): The OS rate in the high-expression groups was significantly lower compared with that in the low-expression groups (P<0.05). In conclusion, the upregulation of CK20, uPA and CRP was found to be a negative prognostic factor for gastric cancer.

Definition of a serum marker panel for glioblastoma discrimination and identification of Interleukin 1β in the microglial secretome as a novel mediator of endothelial cell survival induced by C-reactive protein

Glioblastoma (GBM) is the most common malignant adult primary brain tumor. We profiled 724 cancer-associated proteins in sera of healthy individuals (n=27) and GBM (n=28) using antibody microarray. While 69 proteins exhibited differential abundance in GBM sera, a three-marker panel (LYAM1, BHE40 and CRP) could discriminate GBM sera from that of healthy donors with an accuracy of 89.7% and p<0.0001. The high abundance of C-reactive protein (CRP) in GBM sera was confirmed in 264 independent samples. High levels of CRP protein was seen in GBM but without a change in transcript levels suggesting a non-tumoral origin. Glioma-secreted Interleukin 6 (IL6) was found to induce hepatocytes to secrete CRP, involving JAK-STAT pathway. The culture supernatant from CRP-treated microglial cells induced endothelial cell survival under nutrient-deprivation condition involving CRP-FcγRIII signaling cascade. Transcript profiling of CRP-treated microglial cells identified Interleukin 1β (IL1β) present in the microglial secretome as the key mediator of CRP-induced endothelial cell survival. IL1β neutralization by antibody-binding or siRNA-mediated silencing in microglial cells reduced the ability of the supernatant from CRP-treated microglial cells to induce endothelial cell survival. Thus our study identifies a serum based three-marker panel for GBM diagnosis and provides leads for developing targeted therapies.Biological significanceA complex antibody microarray based serum marker profiling identified a three-marker panel — LYAM1, BHE40 and CRP as an accurate discriminator of glioblastoma sera from that of healthy individuals. CRP protein is seen in high levels without a concomitant increase of CRP transcripts in glioblastoma. Glioma-secreted IL6 induced hepatocytes to produce CRP in a JAK-STAT signaling dependent manner. CRP induced microglial cells to release IL1β which in turn promoted endothelial cell survival. This study, besides defining a serum panel for glioblastoma discrimination, identified IL1β as a potential candidate for developing targeted therapy.

Can CRP affect the blood-brain barrier during acute ischemic stroke?

Abstract Introduction. Ischemic strokes (IS) are one of the main causes of death and disabilities around the globe. Therefore, there is a huge need for researching the pathogenesis of IS. The C-reactive protein (CRP) plays a role during inflammatory processes. Results of some studies conducted on animal models indicate that CRP affects the blood-brain barrier (BBB) stability during IS. The presence of S100BB protein can be considered as an indication of BBB injury. Aim. The purpose of this study was to discover the relationship between CRP and S100BB protein. Material and methods. The study looked at fifty four IS patients, with the disease confirmed by computer tomography (CT). The clinical status was evaluated on the 1st, 3rd, 5th, 10th day and 3 months following the onset of IS. Neurological status was estimated using the National Institute of Health Stroke Scale (NIHSS). Patients’ disability level was determined, using Modified Rankin Scale (mRS) and Barthel Index (BI). The volume of ischemic focus was calculated on the 10th day after the stroke, using CT. The levels of CRP and S100BB were evaluated on 1st, 3rd, 5th and 10th day after the stroke onset with usage of ELISA method. Results. The mean level of CRP and its concentration on the 1st, 3rd, 5th and 10th day directly correlates with a deteriorated clinical status, as measured with the use of NIHSS, BI and mRS on day 10 and 3 months after the onset of IS. We found a correlation with the mean CRP level and bigger volume of ischemic injury. The mean CRP level correlated with the mean level of S100BB protein. In the group of patients with low CRP (0.51-24.68 mg/mL) the level of S100BB and the volume of ischemic focus were lower than in the group with a high level of CRP (24.69-209 mg/mL). Conclusions. CRP can be considered as a predictor of a worse clinical outcome after stroke. The relationship between CRP and S100BB protein can suggest the active role of CRP during IS

Receptor for advanced glycation end products involved in circulating endothelial cells release from human coronary endothelial cells induced by C-reactive protein.

This study was designed to investigate the effect of receptor for advanced glycation end products (RAGE), S100A12 and C-reactive protein (CRP) on the release of circulating endothelial cells (CECs) from human coronary artery endothelial cells (HCAECs). HCAECs were cultured in increasing concentration of CRP (0, 12.5, 25, 50μg/ml) or S100A12 protein (0, 4, 10, 25μg/ml) for 24 hr. CECs were measured by flow cytometry. Small interfering RNA (siRNA) was designed to decrease RAGE level. Fluorescence microscopy and real-time quantitative polymerase chain reaction were used to assess the efficiency of siRNA silencing RAGE. The release of CECs from HCAECs was further evaluated by flow cytometry. CRP caused a significant increase in the release of CECs from HCAECs. The number of CECs increased by about 2-fold in 25 μg/ml CRP-treated group compared to the control group (12.22% compared to 6.82%, P=0.032). But S100A12 failed to increase the release of CECs from HCAECs. Blockade of RAGE by siRNA significantly decreased the release of CECs induced by CRP (13.22% of CRP group compared to 8.77% of CRP+siRNA group, P=0.017). RAGE is involved in the release of CECs induced by CRP, and the effect can be attenuated by silencing RAGE. RAGE may play an important role in endothelial dysfunction in cardiovascular disease. Inhibition of RAGE may be a therapeutic target for coronary artery lesions in Kawasaki disease.

Abstract 35: Common Variants in the CRP Promoter are Associated with a High C-reactive Protein Level in Kawasaki Disease

Kawasaki disease (KD) is an acute self-limiting form of vasculitis that afflicts infants and children and manifests as fever and signs of mucocutaneous inflammation. Children with KD show various laboratory inflammatory abnormalities, such as elevations in their white blood cell (WBC) count, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). We here performed a genome-wide association study (GWAS) of 178 KD patients to identify the genetic loci that influence 10 important KD laboratory markers: WBC count, neutrophil count, platelet count, CRP, ESR, hemoglobin (Hb), aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and total protein. A total of 165 loci passed our arbitrary stage 1 threshold for replication ( p &lt; 1 * 10 -5 ). Of these, only 2 SNPs (rs12068753 and rs4786091) demonstrated a significant association with the CRP level in replication study of 473 KD patients ( p &lt; 0.05). The SNP located at the CRP locus (rs12068753) demonstrated the most significant association with CRP in KD patients (beta = 4.73 and p = 1.20 * 10 -6 according to the stage 1 GWAS; beta = 3.65 and p = 1.35 * 10 -8 according to the replication study; beta = 3.97 and p = 1.11 * 10 -13 according to combined analysis) and explained 8.1% of the phenotypic variation observed. However, this SNP did not demonstrate any significant association with CRP in the general population (beta = 0.37 and p = 0.1732) and only explained 0.1% of the phenotypic variation in this instance. Furthermore, rs12068753 did not affect the development of coronary artery lesions or intravenous immunoglobulin resistance in KD patients. These results indicate that common variants in the CRP promoter can play an important role in the CRP levels in KD.

Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas.

Background:C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells.Methods:CRP immunoreactivity was examined in treatment-naïve HCCs (n=224) using tissue microarrays and was correlated with clinicopathologic parameters. The expression of CRP mRNA and protein was also assessed in 12 HCC cases by quantitative real-time polymerase chain reaction and immunoblotting. Hep3B and SNU-449 HCC cell lines were used for the analysis of CRP mRNA regulation by interleukin 6 (IL-6).Results:CRP was expressed in 133 of 224 HCCs (59.4%) with a variable degree of immunoreactivity (grade 1 in 25.9%; grade 2 in 20.1%; grade 3 in 13.4%). There was an inverse relationship between grade 3 CRP immunoreactivity and cancer-specific survival (p=.0047), while no associations were found with other parameters, including recurrence-free survival. The CRP mRNA expression level was significantly higher in CRP immunopositive cases than in immunonegative cases (p<.05). CRP mRNA expression was increased in Hep3B cells, but was not detected in SNU-449 cells even after IL-6 treatment.Conclusions:We report the expression of CRP in HCC for the first time. CRP expression was associated with poor cancer-specific survival in patients with resectable HCC.

Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat/cholesterol diet.

BackgroundA long-term high-fat/cholesterol (HFC) diet leads to insulin resistance (IR), which is associated with inflammation, atherosclerosis (AS), cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) and nuclear factor ĸB (NF-κB) are involved in the development of IR-AS. Thus, we elucidated the pathological molecular mechanism of IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS.MethodsMale Tibetan minipigs were fed either a normal diet or an HFC diet for 24 weeks. Thereafter, the minipigs were tested for physiological and biochemical blood indices, blood pressure, cardiac function, glucose tolerance, heart rate variability (HRV), and PPAR-associated gene and protein expression levels.ResultsHFC-fed minipigs exhibited IR through increased body weight, fasting blood glucose levels, plasma cholesterol and its composition, and insulin and free fatty acid (FFA) levels; decreased insulin sensitivity; impaired glucose tolerance; and hypertension. Increased C-reactive protein (CRP) levels, cardiac dysfunction, depressed HRV, and the up-regulation of PPAR expression in the abdominal aorta concomitant with down-regulation in the heart tissue were observed in HFC-fed minipigs. Furthermore, the levels of NF-κBp65, IL-1β, TNF-α, MCP-1, VCAM-1, ICAM-1, MMP-9, and CRP proteins were also significantly increased.ConclusionsThese data suggest that HFC-fed Tibetan minipigs develop IR and AS and that PPARs are involved in cardiovascular remodeling and impaired function.

Common variants in the CRP promoter are associated with a high C-reactive protein level in Kawasaki disease.

Kawasaki disease (KD) is an acute self-limiting form of vasculitis that afflicts infants and children and manifests as fever and signs of mucocutaneous inflammation. Children with KD show various laboratory inflammatory abnormalities, such as elevations in their white blood cell (WBC) count, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). We here performed a genome-wide association study (GWAS) of 178 KD patients to identify the genetic loci that influence 10 important KD laboratory markers: WBC count, neutrophil count, platelet count, CRP, ESR, hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and total protein. A total of 165 loci passed our arbitrary stage 1 threshold for replication (p < 1 × 10(-5)). Of these, only 2 SNPs (rs12068753 and rs4786091) demonstrated a significant association with the CRP level in replication study of 473 KD patients (p < 0.05). The SNP located at the CRP locus (rs12068753) demonstrated the most significant association with CRP in KD patients (beta = 4.73 and p = 1.20 × 10(-6) according to the stage 1 GWAS; beta = 3.65 and p = 1.35 × 10(-8) according to the replication study; beta = 3.97 and p = 1.11 × 10(-13) according to combined analysis) and explained 8.1% of the phenotypic variation observed. However, this SNP did not demonstrate any significant association with CRP in the general population (beta = 0.37 and p = 0.1732) and only explained 0.1% of the phenotypic variation in this instance. Furthermore, rs12068753 did not affect the development of coronary artery lesions or intravenous immunoglobulin resistance in KD patients. These results indicate that common variants in the CRP promoter can play an important role in the CRP levels in KD.

Induction of hyperandrogenism in lean reproductive-age women stimulates proatherogenic inflammation.

We determined the effect of hyperandrogenemia as observed in polycystic ovary syndrome (PCOS) on fasting and glucose-stimulated proatherogenic inflammation markers in lean healthy reproductive-age women. Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n=8 each) for 5 days. Interleukin-6 (IL-6) mRNA and IL-6 release from mononuclear cells (MNC), plasma IL-6 and C-reactive protein (CRP), and MNC-derived (matrix metalloproteinase-2) MMP-2 protein were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment. Before treatment, subjects receiving dehydroepinadrosterone (DHEA) or placebo exhibited no differences in androgens, or any proatherogenic inflammation markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate (DHEA-S), and increased the percent change from baseline in fasting IL-6 mRNA, IL-6 release, plasma IL-6, and CRP and MMP-2 protein. However, there were no differences in any of the proatherogenic inflammation markers following glucose ingestion after DHEA administration. We conclude that in lean reproductive-age women, proatherogenic inflammation in the fasting state increases after raising circulating androgens to levels observed in PCOS. However, this hyperandrogenemia-induced MNC activation does not provoke a similar response to subsequent glucose ingestion.

Characterization of the native C-reactive protein (cCRP) and the corresponding liver mRNA in dogs

C-reactive protein (CRP) plays an important role in the acute phase reaction in humans and dogs. For the canine CRP (cCRP) only an in silico deduced preliminary transcript and amino acid sequence is available. The objective of this study was to further characterize the native cCRP protein and its corresponding liver mRNA. Furthermore, immunological similarities of serum CRP in related animal species were investigated. Native cCRP protein was isolated from dog-sera by affinity chromatography and further analyzed by immunodetection, protein sequencing (mass spectrometry and N-terminal Edman sequencing), 2D-gel electrophoresis, and glycoprotein analysis. Furthermore, cCRP cDNA sequence was determined from dog liver total RNA by RT-PCR. Gel electrophoresis, immunodetection and glycoprotein detection revealed two cCRP isotypes with different molecular weights (22 and 25kDa) with the upper band being glycosylated. Selective glycoprotein analysis showed sialic acid terminally linked (2–6) to galactose or N-acetylgalactosamine and subsequent PNGase F treatment identified N-terminal linkage. Mass spectrometry confirmed approximately 45% of the cCRP predicted amino acid sequence and N-terminal amino acid sequencing revealed a shorter native cCRP than expected (204 amino acids). The new canine CRP mRNA sequence confirms 100% of the formerly deduced sequence. Immunological homologies to the canine CRP protein were found in selected dog-related species.This study contributes major molecular details to the knowledge about canine CRP. Such structural information may assist in developing new diagnostic tools for inflammatory-based diseases in dogs as well as other dog-related species.

Ox-LDL upregulates CRP expression through the IGF2 pathway in THP-1 macrophages.

C-reactive protein (CRP) is an acute-phase reactant protein that not only plays a predictive role in determining atherogenesis risk but also represents an active participant in atherogenesis onset and progression. Moreover, an increasing number of studies have reported that oxidized low-density lipoprotein (Ox-LDL) plays a significant role in the initiation and progression of atherosclerosis. However, the effect and underlying mechanism of Ox-LDL on CRP expression remains unclear. THP-1 macrophages were treated with 0, 25, 50, or 100 μg/mL of Ox-LDL for 48 h, or 50 μg/mL of Ox-LDL for 0, 12, 24, and 48 h, respectively. Messenger RNA (mRNA) and protein levels were measured by real-time quantitative PCR and Western blot analysis, respectively. We found that Ox-LDL markedly increased insulin-like growth factor 2 (IGF2) and CRP mRNA and protein levels in a dose- and time-dependent manner in THP-1 macrophages. Treatment with Ox-LDL increased CRP protein expression, and this effect was completely abolished by siRNA-mediated silencing of IGF2 in THP-1 macrophages. Moreover, treatment with pcDNA3.1-IGF2 significantly enhanced CRP protein expression in Ox-LDL-stimulated THP-1 macrophages. CRP expression is upregulated by Ox-LDL through the IGF2 pathway in THP-1 macrophages.

Laparoscopic adjustable gastric banding reduces subcutaneous adipose tissue and blood inflammation in nondiabetic morbidly obese individuals.

Significant and sustained excess weight loss (EWL) appears to reduce the risk of obesity-related comorbidities (insulin resistance, hyperlipidemia, and inflammation), but this has been primarily shown in adult diabetic obese patients. We evaluated whether the EWL obtained 3 years after laparoscopic adjustable gastric banding (LAGB) improves the metabolic phenotype in nondiabetic morbidly obese (NDMO) individuals from south Italy. Serum and subcutaneous adipose tissue (SAT) samples from 20 obese individuals (median BMI=41.5 kg/m(2)) before (T0) and after LAGB (T1) and from 10 controls (median BMI=22.8 kg/m(2)) were taken. Serum leptin, adiponectin, C reactive protein (CRP), and main analyte levels were evaluated by routine methods or immunoassay. In SAT, adipocyte size was measured by hematoxylin/eosin staining, cluster of differentiation 68 (CD68) macrophage infiltration marker by immunohistochemistry, and adiponectin, adiponectin receptors 1 and 2, and interleukin 6 (IL6) messenger RNAs by qRT-PCR. The average EWL was 66.7 %, and CRP, triglycerides, hepatic markers, leptin levels, homeostasis model assessment, and the leptin/adiponectin ratio were lower (p<0.05) at T1 than at T0. The expression of small adipocytes and adiponectin was increased (p<0.05), and inflammation markers (CD68 and IL6) decreased (p<0.05) at T1 vs. T0. At linear regression multivariate analysis, over 90 % (R (2)=0.905) of EWL (dependent variable) was explained by CD68, adiponectinemia, triglyceridemia, CRP, and total protein levels. The EWL obtained 3 years after LAGB resulted in an improvement of lipid metabolism and a reduction of inflammation in NDMO patients, thereby decreasing the risk of obesity-associated diseases.

Developing column material for the separation of serum amyloid P and C reactive protein from biological sources.

In this study, we have investigated the isolation of serum amyloid P (SAP) and C-reactive protein (CRP) from rainbow trout. It has recently been found that SAP is deposited in atherosclerotic lesions or neurofibrillary tangles, which are related to aging process and Alzheimer's disease. Given the importance of CRP, the CRP level in blood is becoming recognized as a potential means of monitoring cardiovascular risk. These two proteins, members of the pentraxin family of oligomeric serum proteins, were isolated from rainbow trout using N-methacryloyl-phosphoserine (MA-pSer) immobilized poly (2-hydroxy ethylmethacrylate) (PHEMA) cryogels as a column material in a fast protein liquid chromatography system. The separation process was verified in two steps. First, SAP and CRP proteins were isolated together from serum sample of rainbow trout using MA-pSer/PHEMA cryogel columns. Second, SAP protein was separated chromatographically from CRP protein using the Ca(2+) ion immobilized PHEMA cryogel column. According to the data, a new and effective technique has been developed for the isolation of SAP and CRP proteins from a biological source, rainbow trout. Finally, purified SAP and CRP were loaded using sodium dodecyl sulfate-polyacrylamide gel and western blot analysis to investigate the purity of chromatographically isolated SAP and CRP compared with commertial SAP and CRP.