Effect of Danzhijiangtang capsule on monocyte chemoattractant protein-1 mRNA expression in newly diagnosed diabetes subclinical vascular lesions

AIM:To investigate the effect of Danzhijiangtang capsule(DJC) on monocyte chemoattractant protein-1(MCP-1) mRNA expression in newly diagnosed type 2 diabetes mellitus(T2DM) subclinical vascular lesions.METHODS:Sixty-two patients with newly diagnosed T2DM subclinical vascular lesions were randomly divided into a control group and treatment group of 31 cases each.Oral antidiabetic therapy with routine western medicine was conducted in both groups,and the treatment group was additionally treated with DJCs.The treatment course for both groups was 12 wk.Before and after treatment,the total efficiency and traditional Chinese medicine(TCM) syndrome score were calculated.The fasting plasma glucose(FPG),2-h plasma glucose(2hPG),fasting insulin(FINS),insulin resistance index(IRI),hemoglobin(Hb)A1c,blood lipids,and hemorheology indices were determined.In addition,the levels of vascular endothelial growth factors including thrombomodulin(TM),von Willebrand factor(vWF),P-selectin and MCP-1 mRNA were determined.RESULTS:After 12 wk of treatment,the TCM syndrome score was significantly decreased compared to before treatment in both groups.After treatment,FPG,2hPG,HbA1c,FINS,IRI,total cholesterol,triglycerides,low-density lipoprotein,high-density lipoprotein,whole blood low shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA were significantly improved compared to before treatment in both groups.After treatment,the total efficiency and TCM syndrome score in the treatment group were better than in the control group.FINS,IRI,whole blood high shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA level in the treatment group were significantly reduced after treatment compared with control group.CONCLUSION:DJCs are efficacious in supplementing qi,nourishing yin and invigorating blood circulation,and upregulate MCP-1 mRNA expression in patients with T2DM subclinical vascular lesions.

Effects of Bifidobacterium infantis on cytokine-induced neutrophil chemoattractant and insulin-like growth factor-1 in the ileum of rats with endotoxin injury

BACKGROUND The digestive tract is the maximal immunizing tissue in the body, and mucosal integrity and functional status of the gut is very important to maintain a healthy organism. Severe infection is one of the most common causes of gastrointestinal dysfunction, and the pathogenesis is closely related to endotoxemia and intestinal barrier injury. Bifidobacterium is one of the main probiotics in the human body that is involved in digestion, absorption, metabolism, nutrition, and immunity.Bifidobacterium plays an important role in maintaining the intestinal mucosal barrier integrity. This study investigated the protective mechanism of Bifidobacterium during ileal injury in rats.AIM To investigate the effects of Bifidobacterium on cytokine-induced neutrophil chemoattractant(CINC) and insulin-like growth factor 1(IGF-1) in the ileum of rats with endotoxin injury.METHODS Preweaning rats were randomly divided into three groups: Control(group C),model(group E) and treatment(group T). Group E was intraperitoneally injected with lipopolysaccharide(LPS) to create an animal model of intestinal injury.Group T was intragastrically administered Bifidobacterium suspension 7 d before LPS. Group C was intraperitoneally injected with normal saline. The rats were killed at 2, 6 or 12 h after LPS or physiological saline injection to collect ilealtissue samples. The expression of ileal CINC mRNA was evaluated by reverse transcription-polymerase chain reaction(RT-PCR), and expression of ileal IGF-1 protein and mRNA was detected by immunohistochemistry and RT-PCR,respectively.RESULTS The ileum of rats in Group C did not express CINC mRNA, ileums from Group E expressed high levels, which was then significantly decreased in Group T(F =23.947, P < 0.05). There was no significant difference in CINC mRNA expression at different times(F = 0.665, P > 0.05). There was a high level of IGF-1 brown granules in ileal crypts and epithelial cells in Group C, sparse staining in Group E, and dark, dense brown staining in Group T. There was a significant difference between Groups C and E and Groups E and T(P < 0.05). There was no significant difference in IGF-1 protein expression at different times(F = 1.269, P > 0.05). IGF-1 mRNA expression was significantly different among the three groups(P < 0.05),though not at different times(F = 0.086, P > 0.05).CONCLUSION Expression of CINC mRNA increased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium reduced CINC m RNA expression. IGF-1 protein and mRNA expression decreased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium prevented the decrease in IGF-1 expression. Bifidobacterium may increase IGF-1 expression and enhance intestinal immune barrier function in rats with endotoxin injury.

Relationship between vitamin D and IL-23,IL-17 and macrophage chemoattractant protein-1 as markers of fibrosis in hepatitis C virus Egyptians

AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 age- and gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at -20?°C. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and -23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjects were included in the study. The mean ± SD were determined, a t-test for comparison of means of different parameters was used. Correlation analysis was done using Pearson’s correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS: The mean vitamin D level in HCV patients (group?I) was 15 ± 5.2 ng/mL while in control (group II) was 39.7 ± 10.8. For active vitamin D in group?I?as 16.6 ± 4.8 ng/mL while in group II was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group?I?and 6.7 ± 2.17 in group II. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group?I?and 216.1 ± 5.38 in group II. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and -23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group?Ia with bright hepatomegaly and included 14 patients. Group?Ib with perihepatic fibrosis and included 11 patients. Group?Ic with liver cirrhosis and included 11 patients. Group?Id with hepatocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001). CONCLUSION: Whether the deficiency of vitamin D is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate.

Effects of Simvastatin on NF-κB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in a Rabbit Model of Atherosclerosis

To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.

Interleukin-1β,Tumor Necrosis Factor-α and Lipopolysaccharide Induce Expression of Monocyte Chemoattractant Protein-1 in Calf Aortic Smooth Muscle Cells

Summary: To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1 ) mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL-1β, 20ng/ml TNF-1α and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4 h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expres- ion of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32 P- end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cul- tured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cul- tured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-1β, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2. 3-fold and 1. 6-fold, respectively). ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9- fold, 1.7-fold and 1.1-fold, respectively). The results suggest that calf aortic SMCs could ex- press MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP-1 mRNA and protein, and the former is more effective than the latter.

Expression of Monocyte Chemoattractant Protein-1 in Monocytes and Effects of Native and Oxidized Very Low Density Lipoproteins

Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capacity of human peripheral blood monocytes to express MCP-1 and effects of native very low density lipoprotein (VLDL) and oxidized VLDL(OX-VLDL) on the expression. The total RNA was extracted from cultured monocytes, which were exposed to VLDL and OX-VLDL, and the media conditioned by monocytes were collected. MCP-1 mRNA expression was examined by Northern blot analysis. MCP-1 protein in conditioned media was determined by using sandwich ELISA. The results showed that monocytes can express MCP-1 after a 24 h incubation at 37℃，and the expression was markedly increased by a exposure to OX-VLDL, whereas the expression was slightly increased when exposed to VLDL. It suggests that the capacity of monocytes to produce MCP-1 that recruits and activates circulating monocytes may be of considerable importance in atherogenesis, and oxidation of VLDL enhances its potential to promote atherogenesis.

InterInterleukin (IL)-4 Induces Production of Cytokine-induced Neutrophil Chemoattractants (CINCs) and Intercellular Adhesion Molecule (ICAM)-1 in Lungs of Asthmatic Rats

Summary： The present study aimed to examine the effect of intedeukin （IL）-4 on neutrophil chemo- taxis in airway inflammation in asthmatic rats and the possible mechanism. Male Wistar rats were intranasally instilled with recombinant rat （rr） IL-4 （rrlL-4） at different doses [2, 4 or 8μ g/animal, dis- solved in 200 μL normal saline （NS）] or rrlL-4 at 4 μg/animal （dissolved in 200 μL NS）. NS （200 μL） and LPS （6 mg/kg/animal, dissolved in 200 IxL NS） were intranasally given respectively in the negative and positive control groups. Moreover, the asthmatic lung inflammation was induced in rats which were then intranasally treated with rrlL-4 （4 μg/animal） or LPS （6 mg/kg/animal）. The normal rats treated with different doses of rrlL-4 and those asthmatic rats were sacrificed 6 h later. And animals instilled with rrlL-4 at 4 μg were sacrificed 6, 12 or 24 h later. The bronchoalveolar lavage fluid （BALF） and lungs were harvested for detection of leukocyte counts by Wright-Giemsa staining and lung histopa- thology by haematoxylin-eosin （HE） staining. The levels of cytokine-induced neutrophil chemoattrac- tant （CINC）-I and intercellular adhesion molecule （ICAM）-I in BALF were determined by ELISA. Real-time PCR was used to measure the mRNA expression of C1NCs （CINC-1, CINC-2u, CINC-2a, CINC-3） and ICAM-1 in lung tissues. The results showed that the intranasal instillation of IL-4 did not induce a recruitment of neutrophils in BALF in rats. However, IL-4 could increase the CINC-1 level in BALF in a dose-dependent manner at 6 h. But the mRNA expression levels of CINC-1, C1NC-2a, CINC-2, CINC-3 were not significantly increased in lungs of IL-4-treated rats relative to NS negative control group. Moreover, IL-4 was found to augment the mRNA expression oflCAM-1 in lungs and the ICAM-1 level in BALF at 6 h. However, the increase in CINC-1 and ICAM-1 levels in BALF of IL-4-treated asthmatic rats was not significantly different from that in untreated asthmatic rats. These findings indicate that IL-4 does not directly recruit neutrophils in the rat lungs, but it may contribute to airway neutrophilia through up-regulation of CINC-1 and ICAM-1.

Correlation of serum cyclophilin A and monocyte chemoattractant protein-1 levels with carotid atherosclerosis in patients with acute cerebral infarction

Objective:To study the correlation of serum cyclophilin A (CyPA) and monocyte chemoattractant protein-1 (MCP-1) levels with carotid atherosclerosis in patients with acute cerebral infarction.Methods: 106 patients with acute cerebral infarction who were hospitalized in our hospital between July 2011 and August 2015 were selected as observation group, and 50 cases of healthy persons who received physical examination in our hospital during the same period were selected as normal control group. The serum CyPA and MCP-1 contnets in two groups were determined. According to the median of CyPA and MCP-1 contents in observation group, they were divided into high CyPA group and low CyPA group as well as high MCP-1 group and low MCP-1 group, 53 cases in each group. Contents of lipid metabolism indexes and carotid atherosclerosis illness-related indicators were compared between acute cerebral infarction patients with different CyPA and MCP-1 contents.Results:Serum CyPA and MCP-1 contents in observation group were significantly higher than those in control group. Serum TC, LP(a) and LDL-C contents in high CyPA group and high MCP-1 group were higher than those in low CyPA group and low MCP-1 group while HDL-C contents were lower than those in low CyPA group and low MCP-1 group. Serum CysC, Hcy and UA contents in high CyPA group and high MCP-1 group were higher than those in low CyPA group and low MCP-1 group.Conclusion: Serum CyPA and MCP-1 contents in patients with acute cerebral infarction are higher than those in normal population, and the contents of CyPA and MCP-1 are positively correlated with the degree of carotid atherosclerosis.

The enhancement of astrocytic-derived monocyte chemoattractant protein-1 induced by the interaction of opiate and HIV tat in HIV-associated dementia

HIV-associated dementia(HAD)is a public health problem and is particularly prevalent in drug abusers.The neuropathogenesis of human immunodeficiency virus(HIV)infection involves a complex cascade of inflammatory events,including monocyte/macrophage infiltration in the brain,glial immune activation and release of neurotoxic substances.In these events,astrocytic-derived monocyte chemoattractant protein-1(MCP-1)plays an important role,whose release is elevated by HIV transactivator of transcription(HIV tat)and could be further elevated by opiates.This review will also consider some critical factors and events in MCP-1 enhancement induced by the interactions of opiate and HIV tat,including the mediating role of mu opioid receptor(MOR)and CCR2 as well as the possible signal transduction pathways within the cells.Finally,it will make some future perspectives on the exact pathways,new receptors and target cells,and the vulnerability to neurodegeneration with HIV and opiates.

Variation of Serum Monocyte Chemoattractant Protein-1 in Patients with Diabetes and Metabolic Syndrome

This study investigated the variation of serum monocyte chemoattractant protein-1（MCP-1） in patients with both diabetes mellitus（DM） and metabolic syndrome（MS）.Based on the International Diabetes Federation（IDF） diagnostic criteria,93 patients enrolled in this study were divided into four groups：normal control（NC）,simple DM,simple MS,and DM plus MS（DM-MS） groups.The main measures included height,weight,waist circumference（WC）,hip circumference,blood pressure,fasting blood glucose,insulin resistance index（HOMA-IR）,serum triglyceride（TG）,HDL-ch,LDL-ch,and MCP-1.The results showed that the serum levels of MCP-1 in the DM-MS group were significantly increased as compared with those in the DM and MS groups（P0.05）,and the increase in the MCP-1 level in the DM group was much higher than in the MS group（P0.05）.The DM-MS group had the highest HOMA-IR levels,followed by MS,DM and NC groups（P0.05）.Correlation tests showed that the association of MCP-1 with age,HDL-ch,or LDL-ch was insignificant,whereas that of MCP-1 with body mass index（BMI）,waist hip rate（WHR）,WC,systolic blood pressure（SBP）,diastolic blood pressure（DBP）,TG,and HOMA-IR was significantly positive.It was concluded that circulating MCP-1 was substantially increased in patients with both DM and MS as compared with that in the patients with DM or MS alone,and the central obese state may contribute to a more vicious proinflammatory condition and insulin resistance in patients with diabetes.

Effect of monocyte chemoattractant protein-1 on chemotactic gene expression by macrophage cell line U937

Objective: To study the chemotactic superfamily genes expression profiling of macrophage line U937 treated with monocyte chemoattractant protein-1 (MCP-1) using gene chip technique. Methods: Total RNA from macrophage line U937 (as control) and U937 with MCP-1 was extracted, made reverse transcript to cDNA and tested with gene expression chip HO2 human. Results: Some chemotactic-related gene expressions were changed in all analyzed genes. Regulated upon activation, normal T cell expressed and secreted (RANTES) was up-regulated over 2-fold and 7 chemotactic-related genes (CCR2, CCR5, CCL16, GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2) were down-regulated over 2-fold in MCP-1 treated U937 cells at mRNA level. Conclusion: MCP-1 can influence some chemokines and receptors expression in macrophage in vitro, in which MCP-1 mainly down-regulates the chemotactic genes expression of those influencing neutrophilic granulocyte (GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2). Another novel finding is that it can also down-regulate the mRNA level of CCR5, which plays a critical role in many disorders and illnesses.

Monocyte chemoattractant protein-1 plays a key role in type 1 diabetes

Type 1 diabetes is an autoimmune dise as e resulting from the selective destruction of β cells in the pa ncreatic islets. In both human and rodent models of type 1 diabetes, the clinica l disease is preceded by a progressive mononuclear cell invasion of the pancreat ic islets (insulitis). In the early stage of insulitis,the major components are monocyte/macrophages, and the recruitment of mononuclear cells is a critical st ep in the pathogenesis of the type 1 diabetes. Studies have revealed that Monocy te chemoattractant protein-1(MCP-1) specifically recruits monocytes/ macrophag es into pancreas and plays an important role in the development of insulitis and diabetes.

Effect of Llinagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy

Objective:To explore the effect of Linagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy.Methods: A total of 98 patients with diabetic nephropathy admitted to the Hospital from January 2017 to September 2018 were enrolled. The patients were divided into two groups according to the random double-blind method, with 49 cases in each group. The control group was treated with Metformin, whereas the experimental group was treated with Linagliptin plus Metformin. After 3 months of continuous treatment, the renal function [urinary albumin excretion rate, 24 h urine protein quantitation and serum creatinine], glycolipids metabolic levels [glycated hemoglobin, fasting blood glucose, total cholesterol and triglycerides], monocyte chemoattractant protein-1, tumor necrosis factor receptor, high-sensitivity C-reactive protein, and adverse reactions were compared between the two groups.Results:After 3 months of treatment, the levels of UAER, 24 h Upor and Scr in the experimental group were shown to be lower than those in the control group, and the difference was statistically significant. After 3 months of treatment, the levels of HbA1c, FPG, TC and TG in the experimental group were shown to be lower than the control group, and the difference was statistically significant. After 3 months of treatment, the levels of MCP-1, sTNFR1 and hs-CRP in the experimental group were lower than those in the control group, and the difference was statistically significant. There was no significant difference in incidence of adverse reactions between the two groups.Conclusion: For patients with diabetic nephropathy, Linagliptin is with higher safety, which can help improve their glycolipids metabolic levels and renal function, reduce the inflammatory response and the levels of MCP-1 and sTNFR1, and yet incur fewer adverse reactions.

Monocyte chemoattractant protein 1 expression in renal tissue is associated w ith monocyte recruitment and tubulo-interstitial lesions in patients with lup us nephritis

Objective To investigate the pattern of monocyte chemoattractant prolein-1 (MCP-1) distribution in the renal interstitium and evaluate its pathogenic role in tubulo-interstitial lesions in patients with lupus nephritis, the distribution of MCP-1 in renal tissue was observed.Methods Eighteen female patients with biopsy-proven lupus nephritis were enrolled in this study. No intensive immunosuppresive therapy was used in these patients during the 3 months prior to renal biopsy. The distribution of MCP-1, infiltration of CD68+ (macrophage/monocyte), CD4+ and CD8+ cells in the tubulo-interstitium of patients with lupus nephritis was detected using immunohistochemical staining with specific antibodies. Renal specimens from patients with minimal change glomerulonephritis were used as controls. Results MCP-1 protein was widely distributed in the renal tissue of patients with lupus nephritis, mainly located at the baso-lateral surface of tubular epithelial cells (16/18 biopsies), and on the wall of interstitial blood vessels (9/18 biopsies). In contrast, tubular MCP-1 staining was weak and rare in renal tissue from controls (7.4±6.2% vs 26.7±22.8%, P<0.01). Tubulo-interstitial infiltration of CD68+, CD4+ and CD8+ cells was markedly increased in patients with lupus nephritis as compared to controls. The tubular expression of MCP-1 was strongly associated with the amount of CD68+ cell infiltration in the interstitium (r=0.5420, P<0.05) and the extent of interstitial fibrosis. There was no correlation between MCP-1 production in tubules and the degree of urinary protein excretion in patients with lupus nephritis (r=0.0547, P>0.05).Conclusions The expression of MCP-1 in the renal tubules and vascular wall was markedly increased in patients with lupus nephritis. The overproduction of MCP-1 in renal tissue may contribute to monocyte recruitment in the interstitium and thus result in tubulo-interstitial damage in lupus nephritis.

Neutrophil chemoattractant receptors in health and disease: double-edged swords

Neutrophils are frontline cells of the innate immune system.These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential.Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis,for inflammation modulation and resolution,wound healing and tissue repair.After fulfilling the appropriate effector functions,however,dampening neutrophil activation and infiltration is crucial to prevent damage to the host.In humans,chemoattractant molecules can be categorized into four biochemical families,i.e.,chemotactic lipids,formyl peptides,complement anaphylatoxins and chemokines.They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs.Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors(GPCRs).In addition,emerging evidence suggests an important role for atypical chemoattractant receptors(ACKRs)that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses.The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation,with a pivotal modulatory role for the(inflammatory)environment.Here,we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease.Depending on the(patho)physiological context,specific chemoattractant receptors may be up-or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences,thus opening new windows for the identification of disease biomarkers and potential drug targets.

Advanced oxidation protein products induce monocyte chemoattractant protein-1 expression via p38 mitogen-activated protein kinase activation in rat vascular smooth muscle cells

Background Advanced oxidation protein products （AOPPs） are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 （MCP-1） is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells （VSMCs）.

Calcitonin gene-related peptide induces proliferation and monocyte chemoattractant protein-1 expression via extracellular signal-regulated kinase activation in rat osteoblasts

Background Calcitonin gene-related peptide （CGRP）, a sensory neuropeptide, affects osteoblast proliferation and bone formation. However, the mechanisms are not fully understood. Monocyte chemoattractant protein-1 （MCP-1） is a chemokine that stimulates the migration of monocytes and plays important roles in regulating bone remolding during fracture repair. In this study, we investigated the effects of CGRP on proliferation and MCP-1 expression in cultured rat osteoblasts. Methods Primary rat osteoblasts were isolated from fetal rats calvariae. Cells were exposed to gradient concentrations （10^-9 to 10^-7 mol/L） of CGRP. Protein and mRNA levels of MCP-1 were quantified by Western blotting and semiquantitative reverse transcdption-polymerase chain reaction, respectively. The protein level of MCP-1 was investigated and compared in cell culture media by enzyme linked immunosorbent assay （ELISA）. Phospho-extracellular signal-regulated kinase （ERK） expression was detected by Western blotting. Cell proliferative activity was measured by 3-（4,5-dimethylthiazol-2-yl）-2, 5-diphenyl tetrazolium bromide （MTT） and BrdU assay. The effects of MAPK/ERK kinase （MEK）-inhibitor U0126 on CGRP-induced MCP-1 expression in primary rat osteoblasts were examined. Results CGRP effectively enhanced primary rat osteoblast proliferation and led to significant increases in the expression of MCP-1 mRNA and protein in time- and dose-dependent manners. CGRP activated the ERK pathway. Pretreatment of cultured rat osteoblasts with MEK inhibitor U0126 resulted in dose-dependent inhibitions of CGRP-induced MCP-1 mRNA and protein levels. Thus, CGRP promoted cell proliferation and stimulated MCP-1 expression in cultured rat osteoblasts. Conclusion These studies document novel links between CGRP and MCP-1 and illuminate the effects of CGRP in regulating bone remodeling.

Urotensin Ⅱ promotes monocyte chemoattractant protein-1 expression in aortic adventitial fibroblasts of rat

Background Urotensin Ⅱ （Ull）,a potent vasoconstrictive peptide,is able to stimulate phenotypic differentiation of adventitial fibroblasts.This study aimed to determine the effect of UII on monocyte chemoattractant protein-1 （MCP1） expression in rat aortic adventitial fibroblasts,so as to explore possible mechanisms in the development of vascular inflammation.Methods Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII （1010-10-7 mol/L） and inhibitors of signal transduction pathways for 1 to 24 hours.MCP-1 mRNA and protein expression and secretion were determined by RT-PCR,Western blotting analysis and enzyme-linked immunosorbent assay （ELISA）,respectively.Results UII dose-and time-dependently promoted MCP-1 mRNA and protein expression and secretion in cells,with maximal effect at 10-8 mol/L at 3 hours for mRNA expression,24 hours for protein expression in the cells,and 12 hours for protein secretion from the cells.Furthermore,the UII effects were significantly inhibited by treatment with its receptor antagonist SB710411,Rho kinase inhibitor Y27632,protein kinase C （PKC） inhibitor H7,mitogen-activated protein kinase inhibitor PD98059,calcineurin inhibitor cyclosporine A,and the Ca2＋channel blocker nicardipine.Conclusion UII may stimulate MCP-1 expression in rat aortic adventitial fibroblasts through its receptor and Rho kinase,PKC,mitogen-activated protein kinase,calcineurin and Ca2＋ channel signal transduction,thus contributing to adventitial inflammation.

Effects of Wenxiao Decoction(稳消方) on the Expression of Interleukin-6,Intercellular Adhesion Molecular-1and Monocyte Chemoattractant Protein-1 in Experimental Atherosclerotic Rabbits

Objective： To observe the effects of different doses of Wenxiao Decoction （稳消方） on the expression of interleukin-6 （IL-6）, intercellular adhesion molecule-1 （ICAM-1）, and monocyte chemoattractant protein-1 （MCP-1） in experimental atherosclerotic rabbits and to explore the mechanism by which it alleviates atherosclerosis. Methods： Sixty New Zealand rabbits were randomly divided into six groups： a blank group, a model group, a Simvastatin group, and high-, medium-, and low-dosage Wenxiao Decoction groups. Except for those in the blank group, all rabbits were fed with a high-cholesterol diet. Carotid atherosclerosis was established by balloon-induced carotid artery endothelium injury in conjunction with the high-cholesterol diet. After 8 weeks, all animals were euthanized to evaluate levels of IL-6 and ICAM-1 expressions （by enzyme linked immunosorbent assay） and of MCP-1 （by immunohistochemistry staining）. Results： The expressions of IL-6, ICAM-1, and MCP-1 were significantly increased in all groups except the blank group （P〈0.05）. However, the rabbits in the Wenxiao Decoction groups and the Simvastatin group showed significantly lower levels of IL-6, ICAM-1, and MCP-1 expression than those in the model group （P〈0.05）. The expressions of IL-6, ICAM-1, and MCP-1 in the high- dosage Wenxiao Decoction group and the Simvastatin group were lower than those in the low-dosage Wenxiao Decoction group （P〈0.05）. The expression of MCP-1 in medium-dosage Wenxiao Decoction group was lower than that in the low-dosage group （P〈0.05）. Conclusions： High, medium, and low doses of Wenxiao Decoction can inhibit the expressions of IL-6, ICAM-1, and MCP-1, which may prevent and stabilize atherosclerotic plaques. There may be a direct relationship between dosage and therapeutic efficacy of Wenxiao Decoction.