2.Mechanism of C-reactive protein on proliferation of multiple myeloma U266 cells.
Yi-Rong YANG ; Ling-Juan HUANG ; Yan-Ping MA ; Yu-Jin LU ; Lin-Hua YANG ; Yong-An ZHOU
Journal of Experimental Hematology 2009;17(5):1242-1245
This study was purposed to investigate the mechanism of C-reactive protein (CRP) on proliferation of U266 cells. The human multiple myeloma cell line U266 was incubated with human CRP (0, 5, 10, 20 mg/L) for 24 hours, then the proliferation level of U266 cells was detected by using blood analyser. The mRNA expressions of survivin and HSP90alpha were examined by RT-PCR. The results showed that the proliferation ratio was increased, as compared with the control group (p<0.05); furthermore, the mRNA levels of survivin and HSP90alpha were up-regulated in proportion to the increased CRP concentrations. There was significant correlation between expression of survivin and HSP90alpha (r=0.737, p<0.0001) in incubated cells. It is concluded that CRP can stimulate the proliferation of MM cells directly by up-regulating the expression of survivin and HSP90alpha in MM cells. CRP can be regarded as a potential target for MM treatment.
Apoptosis
;
C-Reactive Protein
;
metabolism
;
Cell Line, Tumor
;
Cell Proliferation
;
HSP90 Heat-Shock Proteins
;
metabolism
;
Humans
;
Inhibitor of Apoptosis Proteins
;
metabolism
;
Multiple Myeloma
;
metabolism
;
pathology
;
RNA, Messenger
;
genetics
3.Study on the association of the CRP gene +1444C/T polymorphism with symptomatic carotid artery stenosis.
Zhi-zhong LIU ; Xiu-rong DING ; Hua-guang ZHENG ; Guo ZHANG ; Rui-min WANG ; Xi-xiong KANG
Chinese Journal of Medical Genetics 2009;26(4):435-438
OBJECTIVETo investigate the potential association of the C-reactive protein (CRP) gene +1444C/T polymorphism with symptomatic carotid artery stenosis.
METHODSPolymerase chain reaction-restriction fragment length polymorphism was used for the detection of CRP +1444C/T genotypes in 192 patients with symptomatic carotid artery stenosis and 197 healthy controls. Serum high sensitivity-CRP (hs-CRP) levels were measured by routine method.
RESULTSNo TT genotype was detected in this study. Patients with >70% stenosis had higher CC genotype compared with those with <70% stenosis after adjusting for major cerebrovascular risk factors (OR: 2.958; 95% CI: 1.198 - 7.305; P=0.019). CRP levels were significantly higher in patients than in controls. Subgroup analysis according to clinical characteristics (single or double stenosis; >70% or <70% stenosis) did not show difference in CRP levels. There was no significant difference in the prevalence of CT genotype between patients and controls, or between single and double stenosis (P>0.05).
CONCLUSIONThe CRP +1444 CC genotype is a risk factor for >70% carotid artery stenosis. The serum CRP level is associated with the presence of carotid stenosis. However, it is not associated with the number and severity of stenosis.
Aged ; C-Reactive Protein ; genetics ; metabolism ; Carotid Stenosis ; genetics ; metabolism ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Association Studies ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide
4.Effects of 17β-estrogen on expressions of C-reactive protein and its mRNA of vascular smooth muscle cells in rats.
Li XU ; Xinwu ZHANG ; Xiaoming PANG ; Lin CHEN ; Kaige LIU ; Yajun LI
Journal of Zhejiang University. Medical sciences 2013;42(1):86-91
OBJECTIVETo investigate the effects of 17β-estrogen on expressions of C-reactive protein (CRP) and its mRNA in vascular smooth muscle cells(VSMCs).
METHODSImmunocytochemistry was used to detect CRP level in normal VSMCs. The expressions of C-reactive protein and p-ERK1/2 in Ang-II-stimulated VSMCs were evaluated with Western blot. C-reactive protein mRNA was examined with RT-PCR.
RESULTS17β-estrogen had no effect on cell morphology and C-reactive protein expression in normal VSMCs; however, C-reactive protein and mRNA, as well as p-ERK1/2 were decreased in Ang-II-stimulated VSMCs after 17β-estrogen treatment in a concentration-dependent manner.
CONCLUSION17β-estrogen may inhibit the expression of C-reactive protein and its mRNA in Ang-II-stimulated VSMCs via ERK1/2 signal transduction pathway in a concentration-dependent way.
Animals ; C-Reactive Protein ; genetics ; metabolism ; Cells, Cultured ; Estrogens ; pharmacology ; Male ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley
5.Expression of LINC00638 in rheumatoid arthritis patients with damp-heat obstruction syndrome and the regulatory mechanisms for inflammation and oxidative stress.
Yanqiu SUN ; Jian LIU ; Qin ZHOU ; Xiaolu CHEN ; Xiang DING ; Xianheng ZHANG
Journal of Central South University(Medical Sciences) 2022;47(2):183-193
OBJECTIVES:
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint destruction. Both inflammatory response and oxidative stress contribute to the pathogenesis of RA. Oxidative damage can induce and aggravate the imbalance of immune inflammation and promote cell and tissue damage. In this study, the expression of long non-coding RNA (lncRNA) LINC00638 in peripheral blood of patients with RA damp-heat arthralgia syndrome was observed, and the correlation between LINC00638 and disease activity, immune inflammation and oxidative stress indicator was investigated. Subsequently, the mechanisms for LINC00638 in regulating the inflammatory response and oxidative stress in RA fibroblast-like synoviocyte (FLS) under the condition of overexpression and interference were further explored.
METHODS:
In this study, 48 RA patients with damp-heat arthralgia syndrome and 27 normal healthy subjects, who came from Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, were included; and they were divided into a RA group and a control group. The expression of LINC00638 in peripheral blood mononuclear cells (PBMC) from the subjects was detected by real-time PCR. Enzyme linked immunosorbent assay (ELISA) was used to detect serum interleukin (IL)-10, IL-17, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2) expression. Spearman method was used to study the relationship between LINC00638 and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), and to observe the relation between LINC00638 and the Disease Activity Score of 28 Joint (DAS28), Quantitative Score of Damp Heat Syndrome, Visual Analogue Scale (VAS), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). RA-FLS was induced by RA-PBMC, and the RA in vitro cell experimental model was established. LINC00638 overexpression plasmid and small interfering RNA (siRNA) were constructed and transfected into RA-FLS. The cell experiments were divided into 4 groups: a pcDNA3. 1- control group, a pcDNA3.1-LINC00638 group, a siRNA-control group, and a siRNA-LINC00638 group. The transfection efficiency of overexpression plasmid and siRNA was detected by real-time PCR, the expression of TNF-α and IL-10 was detected by ELISA, and the expression of antioxidant proteins HO-1 and SOD2 was detected by immunofluorescence.
RESULTS:
Compared with the control group, the expression of LINC00638 in the RA group was lower (P<0.01). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of LINC00638 was 0.9271. The DAS28 in RA group was 5.70 (5.40-6.50), the Quantitative Score of Damp-heat Syndrome was 20.0 (17.0-23.0), and the VAS score was 7.0 (6.3-8.0). Compared with the control group, the ESR, CRP, RF, anti-CCP, SAS and SDS scores in the RA group were significantly increased (all P<0.01). Spearman correlation analysis showed that: LINC00638 was negatively correlated with ESR (r=-0.532, P<0.01), CRP (r=-0.367, P<0.05), TNF-α (r=-0.375, P<0.01), MDA (r= -0.295, P<0.05), DAS28 (r=-0.450, P<0.01), and which was positively correlated with SOD2 (r=0.370, P<0.05). After the induction of RA-FLS, the expression level of LINC00638 was significantly decreased (P<0.01), indicating that the stimulation of PBMC could effectively reduce the expression of LINC00638 in RA-FLS, so the experimental model of RA-FLS-induced by PBMC was utilized. Compared with the pcDNA3.1-control group, the expressions of LINC00638, IL-10, SOD2, and HO-1 in the pcDNA3.1-LINC00638 group were significantly increased (all P<0.01), and the expression of TNF-α was decreased (P<0.01). Compared with siRNA-control group, LINC00638, IL-10, SOD2 and HO-1 in the siRNA-LINC00638 group were significantly decreased (all P<0.01), and TNF-α was significantly increased (P<0.01).
CONCLUSIONS
LINC00638 is down-regulated in the peripheral blood of RA patients with damp-heat arthralgia syndrome, which is correlated with disease activity, immune inflammation and oxidative stress. Overexpression of LINC00638 can down-regulate pro-inflammatory factors, up-regulate anti-inflammatory factors, and increase antioxidant enzyme activity, thereby improving inflammation and oxidative stress in RA. LINC00638 is the differential lncRNA obtained by the research group's previous high-throughput sequencing of the whole transcriptome of peripheral blood PBMCs in RA patients and validation of clinical samples. In order to deepen the molecular biology research of this gene, the microRNA and mRNA targeted by LINC00638 can be further studied from the perspective of competing endogenous RNAs.
Anti-Citrullinated Protein Antibodies/metabolism*
;
Antioxidants
;
Arthralgia/metabolism*
;
Arthritis, Rheumatoid
;
C-Reactive Protein
;
Hot Temperature
;
Humans
;
Inflammation/genetics*
;
Interleukin-10/metabolism*
;
Leukocytes, Mononuclear
;
Oxidative Stress
;
RNA, Long Noncoding/metabolism*
;
RNA, Small Interfering
;
Tumor Necrosis Factor-alpha/metabolism*
6.Clinical observation and expression of C-reactive protein by LPS-induced A549 cells in patients with chronic obstructive pulmonary disease.
Journal of Central South University(Medical Sciences) 2005;30(2):207-210
OBJECTIVE:
To investigate the level of mRNA expression of C-reactive proteins (CRP) induced by LPS in human alveolar type epithelial cell line, A549.
METHODS:
Sputum and plasma specimens were obtained from patients with chronic obstructive pulmonary disease (COPD) diagnosed according to the national criteria. CRP was measured by enzyme-linked immunosorbent assays (ELISA). A549 cells were incubated with lipopolysaccharide (LPS) at different concentrations and for different time. CRP mRNA was extracted from cells and the expression was analyzed by RT-PCR. The CRP in the supernatant was measured by ELISA.
RESULTS:
The concentration of CRP in the sputum of patients with COPD was significantly higher than that in the plasma (P < 0.05). LPS at different concentrations and for different time induced the expression and secretion of CRP in A549 with a time-dependent increase and the expression of CRP were significantly higher than those of the control (P < 0.05 - 0.01).
CONCLUSION
Self-secretion of CRP in the respiratory tract may exist. A549 induced by LPS may express CRP mRNA.
C-Reactive Protein
;
biosynthesis
;
genetics
;
metabolism
;
Epithelial Cells
;
cytology
;
metabolism
;
Female
;
Humans
;
Lipopolysaccharides
;
Male
;
Middle Aged
;
Pulmonary Alveoli
;
cytology
;
metabolism
;
Pulmonary Disease, Chronic Obstructive
;
metabolism
;
RNA, Messenger
;
biosynthesis
;
genetics
;
Sputum
;
metabolism
7.Combined Effects of Family History of Cardiovascular Disease and Serum C-reactive Protein Level on the Risk of Stroke: A 9.2-year Prospective Study among Mongolians in China.
Zheng Bao ZHU ; Xin Feng HUANGFU ; Chong Ke ZHONG ; Yi Peng ZHOU ; Yun Fan TIAN ; Batu BUREN ; Tian XU ; Ai Li WANG ; Hong Mei LI ; Ming Zhi ZHANG ; Yong Hong ZHANG
Biomedical and Environmental Sciences 2017;30(9):632-640
OBJECTIVEWe aimed to evaluate the combined effect of a family history of cardiovascular disease (CVD) and high serum C-reactive protein (CRP) on the stroke incidence in an Inner Mongolian population in China.
METHODSA prospective cohort study was conducted from June 2002 to July 2012, with 2,544 participants aged 20 years and over from Inner Mongolia, China. We categorized participants into four groups based on the family history of CVD and CRP levels.
RESULTSWe adjusted for age; sex; smoking; drinking; hypertension; body mass index; waist circumference; and blood glucose, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. Compared with the group with no family history of CVD/low CRP levels, the group with family history of CVD/high CRP levels had a hazard ratio (HR) of 1.78 [95% confidence interval (CI), 1.03-3.07; P = 0.039] of stroke, and an HR of 2.14 (95% CI, 1.09-4.20; P = 0.027) of ischemic stroke. The HRs of hemorrhagic stroke for the other three groups were not statistically significant (all P > 0.05).
CONCLUSIONParticipants with both a family history of CVD and high CRP levels had the highest stroke incidence, suggesting that high CRP levels may increase stroke risk, especially of ischemic stroke, among individuals with a family history of CVD.
Asian Continental Ancestry Group ; C-Reactive Protein ; metabolism ; Cardiovascular Diseases ; epidemiology ; genetics ; China ; Genetic Predisposition to Disease ; Humans ; Prospective Studies ; Risk Factors ; Stroke ; epidemiology
8.C-reactive Protein Level, Apolipoprotein B-to-apolipoprotein A-1 Ratio, and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China.
Yun Fan TIAN ; Yi Peng ZHOU ; Chong Ke ZHONG ; Batu BUREN ; Tian XU ; Hong Mei LI ; Ming Zhi ZHANG ; Ai Li WANG ; Yong Hong ZHANG
Biomedical and Environmental Sciences 2016;29(7):467-474
OBJECTIVEWe aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1 (ApoB/ApoA-1) ratio on the incidence of ischemic stroke (IS) or coronary heart disease (CHD) in a Mongolian population in China.
METHODSFrom June 2003 to July 2012, 2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation. All the participants were divided into four subgroups according to C-reactive protein (CRP) level and ApoB/ApoA-1 ratio. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the IS and CHD events in all the subgroups.
RESULTSThe HRs (95% CI) for IS and CHD were 1.33 (0.84-2.12), 1.14 (0.69-1.88), and 1.91 (1.17-3.11) in the 'low CRP level with high ApoB/ApoA-1', 'high CRP level with low ApoB/ApoA-1', and 'high CRP level with high ApoB/ApoA-1' subgroups, respectively, in comparison with the 'low CRP level with low ApoB/ApoA-1' subgroup. The risks of IS and CHD events was highest in the 'high CRP level with high ApoB/ApoA-1' subgroup, with statistical significance.
CONCLUSIONHigh CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population. This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.
Adult ; Apolipoproteins A ; classification ; genetics ; metabolism ; Apolipoproteins B ; genetics ; metabolism ; C-Reactive Protein ; genetics ; metabolism ; Cohort Studies ; Coronary Disease ; epidemiology ; etiology ; Gene Expression Regulation ; Humans ; Mongolia ; epidemiology ; Prospective Studies ; Risk Factors ; Stroke ; epidemiology ; etiology ; Young Adult
9.Effect of C-reactive protein on Notch pathway components in human periphery blood endothelial progenitor cells.
Aihua CHEN ; Fei HE ; Jing CHENG ; Fulin LIU ; Xudong SONG ; Jingbin GUO
Journal of Southern Medical University 2012;32(2):239-242
OBJECTIVETo observe the effect of C-reactive protein (CRP) on the expressions of Notch pathway components in human peripheral blood endothelial progenitor cells (EPC) in vitro.
METHODSMononuclear cells isolated by density gradient centrifugation of human peripheral blood mixed with 6% hydroxyethyl starch (Hes) were plated on fibronectin-coated 6-well culture dishes. After 7 days, the adherent cells were cultured in the presence of 10 and 20 mg/L CRP for 48 h, and the proliferation, migration, and adhesion abilities of the cells were observed. The mRNA expressions of Notch-1 and its ligand Jagged-1 in the EPCs were measured by RT-PCR, and their protein expressions by Western blotting.
RESULTSCRP at 10 and 20 mg/L caused a significant reduction in the number of viable EPCs (61∓3 and 54∓3, respectively) as compared with PBS (71∓4, P<0.05). CRP also resulted in a significant suppression of the proliferation, migration and adhesion capacities of the EPCs. The mRNA and protein expressions of Jagged-1 and Notch-1 in the EPCs significantly increased following CRP exposure in comparison with PBS treatment.
CONCLUSIONCRP can suppress the proliferation, migration and adhesion capacities of the EPCs probably by affecting the expressions of the Notch-1 pathway components.
C-Reactive Protein ; pharmacology ; Calcium-Binding Proteins ; genetics ; metabolism ; Cell Adhesion ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Jagged-1 Protein ; Leukocytes, Mononuclear ; cytology ; metabolism ; Membrane Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Receptor, Notch1 ; genetics ; metabolism ; Serrate-Jagged Proteins ; Signal Transduction ; drug effects ; Stem Cells ; cytology ; metabolism
10.Effect of atorvastatin on lipopolysaccharide-induced expression of C-reactive protein in human pulmonary epithelial cells.
Shangjie WU ; Xiqian XING ; Ye GAN ; Shuiping ZHAO ; Ping CHEN
Journal of Central South University(Medical Sciences) 2009;34(2):104-108
OBJECTIVE:
To determine the effect of atorvastatin on lipopolysaccharide-induced expression of C-reactive protein in cultured A549 cells.
METHODS:
A549 cells were incubated in DMEM medium containing lipopolysaccharide in the absence or presence of various concentrations of atorvastatin. After the incubation, the medium was collected and the level of C-reactive protein was measured by enzyme-linked immunosorbent assay. The cells were harvested and C-reactive protein mRNA was analyzed by reverse transcription polymerase chain reaction.
RESULTS:
Incubation with lipopolysaccharide significantly induced a time and dose dependent increase in the mRNA expression and the production of C-reactive protein in A549 cells (P<0.05). Atorvastatin significantly decreased the lipopolysaccharide induced the mRNA expression and the production of C-reactive protein in a dose dependent manner in A549 cells (P<0.05).
CONCLUSION
Atorvastatin downregulates lipopolysaccharide-induced expression of C-reactive protein in cultured A549 cells, which may be its mechanism of anti-inflammation.
Atorvastatin
;
C-Reactive Protein
;
genetics
;
metabolism
;
Cell Line
;
Down-Regulation
;
drug effects
;
Epithelial Cells
;
metabolism
;
pathology
;
Heptanoic Acids
;
pharmacology
;
Humans
;
Lipopolysaccharides
;
antagonists & inhibitors
;
Lung
;
metabolism
;
pathology
;
Pyrroles
;
pharmacology
;
RNA, Messenger
;
genetics
;
metabolism