C-reactive protein induces pro- and anti-inflammatory effects, including activation of the liver X receptor α, on human monocytes

2008 ◽  
Vol 99 (03) ◽  
pp. 558-569 ◽  
Author(s):  
Armelle Ropars ◽  
Carole Seguin-Devaux ◽  
Gaël Poitevin ◽  
Sandrine Grosjean ◽  
Vèronique Latger-Cannard ◽  
...  

SummaryNon-specific markers of inflammation such as C-reactive protein (CRP) are associated statistically with an increased risk of atherosclerosis through mechanisms that have not yet been fully elucidated.We investigated the effects of CRP on several aspects of human monocyte biology, a cell type involved in the initiation and progression of atherosclerosis. Blood monocytes isolated from healthy men and premenopausal women (n=9/group) were exposed to purified CRP (25 μg/ml) for 12 hours. Changes in gene expression were analyzed using a custom-made array containing oligonucleotide sequences of 250 genes expressed by activated monocytes and confirmed by quantitative PCR. CRP increased significantly the expression of the cytokines interleukin (IL)-1α, IL-1β and IL-6, and the chemokines GRO-α, GRO-β and IL-8. CRP also displayed anti-inflammatory effects through upregulation of liver X receptor (LXR) α and activin receptor expression, and down-regulation of alpha 2-macroglobulin expression. Increased LXRα mRNA expression in both monocytes and the monocytic cell lineTHP-1 was associated with increased LXRα protein expression and nuclear translocation, as well as increased ABCA1 mRNA expression, a target gene of LXRα. Western Blot analysis revealed CRP-induced nuclear translocation of NF-κB and activation of p42/44, MAP and Akt kinases. CRP-induced LXRá mRNA expression was inhibited by anti-CD64 (FcγRI) antibodies and by p42/44 and PI3 kinase inhibitors. This hypothesis-generating study demonstrates that CRP modulates the expression of genes that contribute to both pro- and anti-inflammatory responses in human monocytes. Among these novel anti-inflammatory effects, we show clearly that CRP activates the LXRα pathway.

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4188-4194 ◽  
Author(s):  
Robert Kleemann ◽  
Lars Verschuren ◽  
Bert-Jan de Rooij ◽  
Jan Lindeman ◽  
Moniek M. de Maat ◽  
...  

Abstract Inflammatory processes, aside from cholesterol, play a central role in atherogenesis. Human C-reactive protein (huCRP) signals systemic inflammation and independently predicts future cardiovascular risk. Cholesterol-lowering statins reduce atherosclerosis and plasma huCRP levels. Evidence is sought for a direct anti-inflammatory statin effect in vivo, independent of effects on plasma cholesterol and atherogenesis. The effect of atorvastatin and simvastatin on huCRP expression was studied in nonatherosclerotic huCRP transgenic mice and compared with another class of hypolipidemic drugs, peroxisome proliferator-activated receptor-alpha (PPARα) activators, notably fenofibrate and Wy14643. Like statins, PPARα activators combine antiatherosclerotic properties with huCRP-lowering effects. Dietary treatment with statins or PPARα activators decreased basal and interleukin-1β (IL-1β)-induced plasma huCRP levels independently of cholesterol lowering. These direct anti-inflammatory in vivo effects occurred at the transcriptional level and could be confirmed in cultured human liver slices and in human hepatoma cells transiently transfected with a huCRP promoter-driven luciferase reporter. A molecular rationale for the suppression of IL-1-induced huCRP transcription is provided by showing that statins and PPARα activators up-regulate IκBα protein expression. This results in a reduced nuclear translocation of p50-nuclear factor κ B (NFκB) and thereby decreased amounts of nuclear p50-NFκB∼CCAAT/enhancer binding protein beta (C/EBPβ) complexes, which determine the huCRP transcription rate. Our results provide conclusive evidence for a direct suppressive effect of statins and PPARα activators on huCRP expression independent of cholesterol lowering and atherogenesis. (Blood. 2004;103:4188-4194)


2011 ◽  
Vol 10 (2) ◽  
pp. 207
Author(s):  
Hemelrijck M.J.J. Van ◽  
I. Jugner ◽  
G. Walldius ◽  
H. Garmo ◽  
E. Binda ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Makrouhi Sonikian ◽  
Aggeliki Barbatsi ◽  
Eugenia Karakou ◽  
Theodoros Chiras ◽  
Jacob Skarakis ◽  
...  

Abstract Introduction C-reactive protein (CRP) and procalcitonin (PCT) are widely used as markers of inflammation and infection in general population and in chronic hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT levels may be elevated even in the absence of inflammatory or infectious disease and diagnostic process is a challenge in such cases. We studied HD patients' laboratory profile concerning CRP and PCT. Subjects and Methods We studied 25 stable HD patients, M/F=22/3, aged 68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,44±0,3 and no signs of infection. Patients were classified in two groups. Group A included 10 patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 patients on conventional HD with low-flux polysulfone membrane. Twenty healthy subjects formed a control group C. Serum CRP and PCT levels were measured in duplicate in A and B groups before and at the end of mid-week dialysis sessions and also in C group. Results Pre-D serum CRP values in the total of patients were higher than those in healthy controls (10,89±19,29 vs 2,54±1,28 mg/L-p=0,004). Compared with group C, pre-D CRP values were higher only in B group (15,98±24,54 mg/L-p=0,001) but not in A group (4,09±3,33 mg/L-p=NS). There was a significant difference in pre-D serum CRP values between A and B groups (p=0,028). At the end of D session serum CRP values showed a tendency to increase in both groups A (5,16±4,81 mg/L) and B (17,00±27,00 mg/L) but differences were not significant. Pre-D serum PCT values in the total of patients were higher than those in healthy controls (0,82±0,9 vs 0,29±0,55 ng/ml-p<0,001). Compared with group C, pre-D PCT values were higher in both A group (0,52±0,15 ng/ml-p<0,001) and B group (1,01±1,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT values between A and B groups (p=0,261). At the end of D session serum PCT values decreased in A group (0,32±0,11 ng/ml-p<0,001) and increased in B group (1,12±1,21 ng/ml-p=0,014). Conclusions In patients on both conventional low-flux HD and online HDF pre-D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis modality and membrane flux did not affect post-D serum CRP values, but post-PCT values decreased in online HDF. PCT usefulness might be limited in dialysis with high-flux membranes. Cut-off values have to be established for both markers to eliminate confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed patients.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Toshiyuki Takahashi ◽  
Toshihisa Anzai ◽  
Hidehiro Kaneko ◽  
Atsushi Anzai ◽  
Yoshinori Mano ◽  
...  

We have previously reported that elevated serum C-reactive protein (CRP) level after acute myocardial infarction (MI) is associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling and cardiac death. Recent experimental studies have shown that CRP per se has some biological properties including proinflammatory and proapoptotic effects, suggesting a pathogenetic role of CRP in the remodeling process after MI. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI through some deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their nontransgenic littermates (Control) underwent proximal ligation of the left coronary artery. Despite increased serum CRP level and cardiac CRP expression in CRP-Tg mice, there was no difference in phenotype between CRP-Tg and control mice before MI. Mortality at five weeks after MI was not different between groups (CRP-Tg: 49%, n=35; Control: 38%, n=40, P =0.28). Five weeks after MI, echocardiography showed that CRP-Tg mice had more LV dilation (LVEDD, CRP-Tg: 5.8 ± 0.1 mm, n=14; Control: 5.2 ± 0.1 mm, n=17, P =0.002) and worse LV function (EF, CRP-Tg: 13 ± 2%, n=14; Control: 19 ± 1%, n=17, P =0.01). Hemodynamic studies indicated that LV +dP/dt (CRP-Tg: 2,947 ± 480 mmHg/s, n=9; Control: 3,788 ± 656 mmHg/s, n=10, P =0.02) and -dP/dt (CRP-Tg: −2,230 ± 48 mmHg/s, n=9; Control: −2,890 ± 161 mmHg/s, n=10, P =0.003) were lower in the CRP-Tg group than in the Control group, although infarct size was comparable. Histological evaluation at one week after MI showed a higher rate of apoptosis in the border zone of infarcted hearts from CRP-Tg mice (CRP-Tg: 1,434 ± 322 per 10 5 nuclei; Control: 596 ± 112 per 10 5 nuclei, n=6 for each, P =0.03). Quantitative RT-PCR showed that angiotensin II type 1a receptor and interleukin-6 were upregulated in viable LV samples from CRP-Tg mice compared with controls. Increased CRP expression exacerbates LV dysfunction and remodeling after MI, associated with increased apoptotic rates, increased angiotensin II receptor expression and exaggerated inflammatory response.


2021 ◽  
Vol 5 (1) ◽  
pp. 40
Author(s):  
Livia Kurniati Saputra ◽  
Dian Novita Chandra ◽  
Ninik Mudjihartini

Low grade inflammation has been recognized of being involved in the pathogenesis of chronic disease pandemic. Individual lifestyle plays a major role in the development of low grade inflammation. Sedentary workers are at risk of low grade inflammation due to the nature of their work. Dietary habit also contributes to inflammatory status in the body. Dietary fiber intake indirectly affects the immune system. It has been hypothesized that fiber has anti-inflammatory effects, both body weight-related and body weight-unrelated This review will focus more on body weight-unrelated anti-inflammatory effect of fiber, especially through fiber’s fermentation metabolites, the short chain fatty acid (SCFA). Its anti-inflammatory effect can be seen by monitoring a biomarker of inflammation in the body, the high sensitivity C-reactive protein (hsCRP). This review’s objective is to cover the mechanisms and role of dietary fiber intake on serum hsCRP level as a marker of low grade inflammation on sedentary workers. 


2021 ◽  
Vol 17 (1) ◽  
pp. 24-28
Author(s):  
M.V. Кhaitovych ◽  
L.M. Voroniuk ◽  
G.Yu. Borisova ◽  
N.V. Diudenko ◽  
N.M. Miagka

Relevance. In 2020, children were hospitalized with fever and multisystem inflammation throughout the world during the COVID-19 pandemic. In the United States, this condition is called MIS-C (Multisystem Inflammatory Syndrome in Children). This syndrome is thought to be similar to the severe course of COVID-19 in adults (cytokine storm). The objective of the work is to evaluate the features of the course and pharmacotherapy of multisystem inflammatory syndrome in children. Materials and methods. The study included 17 children (10 boys and 7 girls) aged 3-16 years (on average – 9.5±3.4 years). Diagnosis of coronavirus infection was performed by polymerase chain reaction with real-time detection, determined the level of immunoglobulins M and G before coronavirus infection. Results. The duration of fever in patients was 5-21 days (average 8.1±4.0 days), the duration of inpatient treatment – 7-35 days (average 15.7±7.0 days). Blood albumin levels were reduced in 53.8% of children; the level of fibrinogen was increased in 88.2% of children, the level of C-reactive protein, ferritin, and D-dimer – in all patients. 15 (88.2%) children had pathology of the digestive system, 13 (76.5%) – cardiovascular system (7 children were diagnosed with carditis, 2 – dilation of coronary arteries, 7 – cardiac arrhythmia). Acute respiratory distress -syndrome was found in a 13-year-old girl, shock - in an 11-year-old boy, 11 children (64.7%) were diagnosed with the pathology of the respiratory system (pleurisy, pneumonia), skin and mucous membranes, and 4 children (23.5%) there were manifestations of central nervous system disorders (meningism, decreased reflexes, ataxia), in 2 (11.8%) – renal failure. On average, each patient had lesions of 3.9 ±1.2 systems. Conclusions. MIS-C was manifested by prolonged fever, high levels of laboratory markers of inflammation, hypoalbuminemia, hypercoagulation, often – pathological manifestations of the cardiovascular, digestive, respiratory systems, skin, and mucous membranes. The treatment included intravenous immunoglobulin, steroids, anticoagulant, and antibacterial therapy and was effective.


2019 ◽  
Vol 5 (1) ◽  
pp. 45-52
Author(s):  
Pavel D. Kolesnichenko ◽  
Anna A. Peresypkina ◽  
Artem A. Poromov ◽  
Elena N. Kareva ◽  
Alexey N. Demidenko

Introduction: Evaluation of anti-inflammatory action of Codelac® Broncho with Thymus Serpyllum (elixir) in comparison with Fenspiride was carried out on the model of acute carrageenan inflammation of the paws in rats. Materials and methods: Edema was caused by subplantar injection of 0.1 ml of 1% λ- carrageenan gel into the hind paw. The severity of edema was assessed by using 37140 plethysmometer (UGO BASILE, Italy). The measurements were performed before edema induction and 1, 2, 4, 12, 24, 48, 72, 96 and 120 hours afterwards. Anti-inflammatory activity of the drugs was also evaluated based on the analysis of rats’ blood, C-reactive protein concentration and histological examination results. Results and discussion: A decrease in the paw volume increment was revealed in the group with the studied drug in comparison with the group with the carrageenan edema model (control) 4, 12, 24 hours after injection of carrageenan (p<0.05). As a result of plethysmometry, a more pronounced anti-inflammatory effect of the studied drug than that of Fenspiride was revealed. There was a significant decrease in the levels of leukocytes (p<0.05), lymphocytes (p<0.05), monocytes (p<0.05) and neutrophils (p<0.05) in the group with the studied drug compared to those the the control 48 hours after the initiation of edema, while in the group with Fenspiride, there was only a decrease in the levels of leukocytes (p<0.05) and lymphocytes (p<0.05). There were no differences in the concentration of C-reactive protein between the groups. Conclusion: The obtained data indicate a more pronounced anti-inflammatory activity of Codelac® Broncho with Thymus Serpyllum in comparison with Fenspiride, on the model of acute carrageenan inflammation of the paw in rats.


2019 ◽  
Vol 77 (6) ◽  
Author(s):  
Mariam Onsy F Hanna ◽  
Asmaa M Abdelhameed ◽  
Amany A Abou-Elalla ◽  
Reem M Hassan ◽  
Inas Kostandi

ABSTRACT Understanding the complex immune responses in sepsis is crucial to provide insight into the clinical syndrome. We evaluated the changes in the surface receptors of the cells of innate immunity, neutrophils and monocytes, in patients with sepsis. Since sepsis remains a clinical challenge, we aimed to assess the significance of altered receptor expression in diagnosis and prognosis. Critically ill patients with sepsis (n=31) were investigated for the expression of receptors for IgG heavy chain CD64 and CD16 on neutrophils and CD64 and the lipopolysaccharide receptor CD14 on monocytes by flow cytometry and compared to 23 patients with no sepsis. Patients with sepsis had increased expression of neutrophil CD64. Neutrophil CD64 was specific for discriminating patients with sepsis but showed weak sensitivity. When integrated in a scoring system, neutrophil CD64 in combination with C-reactive protein (CRP) and SOFA score showed a diagnostic accuracy of 0.93 for sepsis and significantly predicted increased mortality risk. While neutrophil CD16 did not discriminate for sepsis, decreased expression was associated with increased mortality risk. In contrast, monocyte CD64 and CD14 expression was unaltered in sepsis and was not associated with mortality risk. Our study demonstrates that unlike monocytes, neutrophil receptor expression is altered in patients with sepsis receiving intensive care. It is promising to apply a combination approach to diagnose sepsis especially in time-limited conditions.


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