High Glucose Upregulates C-Reactive Protein Synthesis in Macrophages

Kaplan, Marielle; Tendler, Y; Mahamid, Riad; Shiner, Maayan; Aviram, Michael; Hayek, Tony

doi:10.1373/clinchem.2009.136838

Cited by 17 publications

(12 citation statements)

References 6 publications

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“…Most importantly, in the current context, CRP also promotes proinflammatory cytokine production (31), leading to mesangial cell proliferation, matrix overproduction, and increased vascular permeability resulting in albuminuria (32). Human and murine macrophages exposed to high glucose concentrations show increased levels of CRP mRNA and protein biosynthesis and secretion, suggesting that CRP-mediated proinflammatory effects could be triggered locally by macrophage-produced CRP in addition to the effect of circulating and liver-derived CRP (33). It has also been demonstrated that CRP promotes the differentiation of human monocytes toward a proinflammatory phenotype (34) and induces macrophage colony–stimulating factor release via upregulation of NF-κB, resulting in increased macrophage recruitment and proliferation (35).…”

Section: Discussionmentioning

confidence: 99%

Association of Race/Ethnicity, Inflammation, and Albuminuria in Patients With Diabetes and Early Chronic Kidney Disease

et al. 2014

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OBJECTIVEAfrican Americans (AAs) and Hispanics have higher diabetes and end-stage renal disease but similar or lower early chronic kidney disease (CKD) compared with whites. Inflammation plays a critical role in the pathogenesis of diabetes-related CKD. We postulated that in contrast to the general population, AAs and Hispanics have a higher prevalence of early diabetic CKD and systemic inflammatory markers compared with whites.RESEARCH DESIGN AND METHODSWe analyzed the National Health and Nutrition Examination Survey 1999–2008 of 2,310 diabetic patients aged ≥20 years with fasting plasma glucose (FPG) ≥126 mg/dL. We performed multiple linear regression among patients with early CKD (urinary albumin excretion [UAE] ≥30 μg/mL and estimated glomerular filtration rate ≥60 mL/min/1.73 m2) to test the relationship between UAE and C-reactive protein (CRP) by race/ethnicity, adjusting for demographics, diabetes duration, FPG, hemoglobin A1c, uric acid, white blood cell count, medication use, cardiovascular disease, and related parameters.RESULTSIn patients with diabetes, the prevalence of early CKD was greater among Hispanics and AAs than whites (P < 0.0001). AAs had higher adjusted odds ratio (AOR) for CRP ≥0.2 mg/dL (AOR 1.81 [95% CI 1.19–2.78]), and Hispanics had higher AOR for UAE ≥30 μg/mL (AOR 1.65 [1.07–2.54]). In a regression model adjusted for confounding variables, there was a significant association between UAE and CRP in the mid-CRP tertile (CRP 0.20–0.56 mg/dL, P = 0.001) and highest CRP tertile (CRP ≥0.57 mg/dL, P = 0.01) for Hispanics, but only in the mid-CRP tertile (P = 0.04) for AAs, compared with whites.CONCLUSIONSAAs and Hispanics with diabetes have a higher prevalence of early CKD compared with whites, which is significantly associated with UAE and/or CRP.

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Section: Discussionmentioning

confidence: 99%

Association of Race/Ethnicity, Inflammation, and Albuminuria in Patients With Diabetes and Early Chronic Kidney Disease

et al. 2014

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“…The GTEx database 36 found a median of 6,975 CRP transcripts per million, from 175 hepatic samples, only "outlier" values from pancreas and spleen, and no transcripts for whole blood. Of primary concern to the present study, the mRNA expression of CRP by leukocytes has been definitively reported 12,37 ; but uncertainty remains as to whether this occurs to a significant extent in a non-stimulated state 9,15,38,39 .…”

Section: Discussionmentioning

confidence: 91%

Unactivated leukocyte expression of C-reactive protein is minimal and not dependent on rs1205 genotype

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Martell

et al. 2021

Sci Rep

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C-reactive protein (CRP), a prominent component of the innate immune system, is implicated in the pathophysiology of many conditions. CRP production primarily occurs in the liver; but contributions from other tissues is unclear. The Genotype-Tissue Expression Portal shows essentially no expression in whole blood and reports in the literature are conflicting. Multiple genomic variants influence serum levels of CRP. We measured CRP mRNA expression in leukocytes and sought to determine if rs1205 genotype influences leukocyte expression. Leukocytes were obtained from 20 women differing by genotype. Quantitative, real-time PCR (RT-qPCR) detected CRP and reference gene (GAPDH) mRNA. Leukocyte expression was calculated by the 2ΔCT method, and against a standard curve. Digital drop PCR was also used to calculate expression ratios. Student's t test and linear regression methods examined possible differences between genotypes. During 32 runs (10 replicates each), the RT-qPCR mean (SD) CRP/GAPDH ratio was 3.39 × 10–4 (SD 1.73 × 10–4) and 3.15 × 10–4 (SD 1.64 × 10–4) for TT and CC genotypes respectively, p = 0.76; and digital drop PCR results were similar. Serum CRP was not significantly different between genotypes, nor correlated with leukocyte expression. CRP is minimally expressed in unactivated leukocytes and this expression is not likely influenced by rs1205 genotype.

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“…Therefore, these variables may not have the ability to predict the further changes in glycaemic status. Moreover, the situation may also be further complicated by the finding of a recent study, showing that hyperglycaemia could increase CRP secretion from human macrophages [35]. …”

Section: Discussionmentioning

confidence: 99%

Evaluation of the combined use of adiponectin and C-reactive protein levels as biomarkers for predicting the deterioration in glycaemia after a median of 5.4 years

Tso

Law

et al. 2011

Diabetologia

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Aims/hypothesisHypoadiponectinaemia and raised C-reactive protein (CRP) level are obesity-related biomarkers associated with glucose dysregulation. We evaluated the combined use of these two biomarkers in predicting the deterioration of glycaemia in a prospective study after a median of 5.4 years.MethodsIn total 1,288 non-diabetic participants from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, with high-sensitivity CRP (hsCRP) and total adiponectin levels measured were included. OGTT was performed in all participants. Two hundred and six participants had deterioration of glycaemia at follow-up, whereas 1,082 participants did not.ResultsBaseline age, hsCRP and adiponectin levels were significant independent predictors of the deterioration of glycaemia in a Cox regression analysis after adjusting for baseline age, sex, BMI, hypertension, triacylglycerols, 2 h post-OGTT glucose and homeostasis model assessment of insulin resistance index (all p < 0.01). The introduction of hsCRP or adiponectin level to a regression model including the other biomarker improved the prediction of glycaemic progression significantly in all participants, especially in women (all p < 0.01). The combined inclusion of the two biomarkers resulted in a modest improvement in model discrimination, compared with the inclusion of either one alone. Among participants with impaired fasting glucose/impaired glucose tolerance (IFG/IGT) at baseline, hsCRP and adiponectin levels were not predictive of progression or improvement of glycaemic status.Conclusions/interpretationAdiponectin and hsCRP levels are independent factors in predicting the deterioration of glycaemia, supporting the role of adiposity-related inflammation in the development of type 2 diabetes. Their combined use as predictive biomarkers is especially useful in women, but not in participants with IFG/IGT.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2227-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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High Glucose Upregulates C-Reactive Protein Synthesis in Macrophages

Cited by 17 publications

References 6 publications

Association of Race/Ethnicity, Inflammation, and Albuminuria in Patients With Diabetes and Early Chronic Kidney Disease

Association of Race/Ethnicity, Inflammation, and Albuminuria in Patients With Diabetes and Early Chronic Kidney Disease

Unactivated leukocyte expression of C-reactive protein is minimal and not dependent on rs1205 genotype

Evaluation of the combined use of adiponectin and C-reactive protein levels as biomarkers for predicting the deterioration in glycaemia after a median of 5.4 years

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