Monocyte Chemoattractant Protein-1 Concentrations Research Articles

Serum levels of monocyte chemoattractant protein-1 in periodontal health and disease

Objectives: Initial research has reported high levels of monocyte chemoattractant protein-1 (MCP-1) in gingival crevicular fluid (GCF) of periodontitis patients. Present study has been carried out to assess its concentration in serum and to find its association with periodontal health and disease. Design: 60 subjects were divided into three groups ( n = 20) based on gingival index (GI), probing pocket depth (PPD) and clinical attachment loss (CAL): healthy (group I), gingivitis (group II) and chronic periodontitis (group III). A fourth group (group IV) consisted of 20 subjects from group III, 6–8 weeks after treatment [i.e. scaling and root planing (SRP)]. Serum samples obtained from each patient were quantified for MCP-1 using enzyme-linked immunosorbent assay (ELISA). Results: The mean MCP-1 concentration in serum was found to be the highest in group III i.e. 465.80 pg/ml and lowest in group I i.e. 155.20 pg/ml. For group II (251.60 pg/ml) and group IV (263.20 pg/ml) the mean MCP-1 concentrations were found to lie in between the concentrations obtained in group I and III. Conclusions: Serum MCP-1 concentration was found to be, approximately one and half folds higher in gingivitis patients (group II) and three folds higher in chronic periodontitis patients (group III) as compared to healthy subjects (group I). Further, the MCP-1 concentration increased proportionally with the severity of disease in group II and III showing positive correlation with clinical parameters. Thus, its role as an inflammatory biomarker in periodontal disease can be proposed.

Effects of an Antagonist of the Gastrin-Releasing Peptide Receptor in an Animal Model of Uveitis

Some studies have shown the role of gastrin-releasing peptide (GRP) on the production and release of cytokines both in animal models and in humans with inflammatory diseases, but there are no reports on the effects of GRP in ocular inflammatory disease, mainly uveitis. The authors report on the effects of the GRP receptor (GRPR) antagonist RC-3095 in a well-established model for uveitis induced by the administration of lipopolysaccharide (LPS), comparing its effects with those of glucocorticoids. Adult male Wistar rats (weight range, 250-300 g; n = 6 per group) were randomly divided into four groups: saline, LPS + saline, LPS + dexamethasone, LPS + RC-3095. Two hours after LPS administration, RC-3095 (0.3 mg/kg, single dose, subcutaneously) or dexamethasone (1 mg/kg, each 6 hours, subcutaneously) was administered. After 24 and 48 hours, rats were anesthetized, aqueous humor was sampled, and the irides were removed. Aqueous humor tumor necrosis factor-alpha, monocyte chemoattractant protein-1 concentration, myeloperoxidase activity were determined. In addition, oxidative damage to the irides was determined by the measure of thiobarbituric acid reactive substances and protein carbonyl content. The acute administration of RC-3095 exhibited anti-inflammatory actions, characterized by a reduction of myeloperoxidase activity and a decrease in tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels, to a greater extent than dexamethasone. In addition, RC-3095 elicits important action against irides oxidative damage. These findings suggest that GRP participates in the inflammatory response in an animal model of uveitis, making GRPR a target for new therapeutic options in the treatment of uveitis.

The effects of testosterone on the expression of inflammatory factors in 3T3-L1 adipocytes and its mechanism

To explore the effects of androgen upon the production of inflammatory Cultured factors in 3T3-L1 adipocytes and to investigate the mechanism at the molecular level. pre-adipocytes from 3T3-L1 cell line were induced to differentiate into adipocytes. Mature adipocytes were treated with testosterone at a concentration of 10(-9) to 10(-15) mol/L for either short (0 to 30 min) or long (12, 24 and 48 h) treatment course. Secretion of inflammatory factors, i.e., interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), in the culture medium were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-6 and MCP-1 were determined by reverse transcriptase PCR. Phosphorylation of NF-KB was analyzed by Western blot with beta-actin as the reference gene. In another experiment, adipocytes were manipulated according to the same protocol except being pretreated with PDTC (inhibitor of NF-KB) for 2 h prior to the addition of testosterone. The results of two experiments were compared. (1) The secretion of IL-6 and MCP-1 in the culture medium were higher in the testosterone-treated groups than in the control groups (P < 0.05). The highest concentration of IL-6 and MCP-1 were observed in the group treated with 10(-5) M testosterone for 24 h. The mRNA expression of IL-6 and MCP-1 were higher in the groups treated with testosterone for 12 h, especially with testosterone of 10(-5) mol/L; (2) With a short treatment course of testosterone, more NF-kappaB were phosphorylated than in control, especially with testosterone of 10(-5) mol/L. More NF-kappaB was phosphorylated following the 12 h testosterone treatment (10(-9), 10(-7) and 10(-5) mol/L), especially with a testosterone concentration of 10(-9) and 10(-5) mol/L. (3) When pretreated by NF-kappaB inhibitor and followed by 10(-5) mol/L testosterone for 24 h, the secretion of IL-6 and MCP-1 in the culture medium decreased significantly (P < 0.01). Likewise, when pretreated by NF-kappaB inhibitor and followed by 10(-5) M testosterone for 12 h, the mRNA expression of IL-6 and MCP-1 decreased significantly. Within the certain scope, testosterone could increase the expression of inflammatory factors in adipocytes through the activation of NF-kappaB.

Serum IL-8 and MCP-1 Concentration Do Not Identify Patients With Enlarging Contusions After Traumatic Brain Injury

Cerebral contusions contain numerous leukocytes, and a temporal relationship exists among cerebral chemokine expression, leukocyte recruitment, and contusion enlargement. This would suggest a role for chemokines in contusion development. However, it has not been established if serum concentrations of chemokines such as interleukin-8 (IL-8) or monocyte chemoattractant protein-1 (MCP-1) change with contusion enlargement. Eighteen adult patients with severe contusional traumatic brain injury, on computerized tomography, were identified. Patients with diffuse injuries or extradural and subdural hematomas associated with mass effect were not included in the study. Daily serum samples were taken for the measurement of IL-8 and MCP-1 concentrations for up to 11 days postinjury. In the patients who died while in intensive care, IL-8 and MCP-1 were significantly greater than in those patients discharged (18 [0-202] vs. 0 [0-156] pg/mL and 498 [339-1,063] vs. 368 [86-11,289] pg/mL for IL-8 and MCP-1, respectively). No difference was seen in serum chemokine levels in patients who deteriorated with contusion enlargement compared with those that did not. The IL-8 and MCP-1 concentrations did not change significantly over time either in the group as a whole or in the subgroup of patients who deteriorated. These inflammatory mediators may be predictive of a poor outcome in patients with traumatic brain injury in which contusions are the predominant abnormality. However, they do not distinguish those patients who will deteriorate because of contusion enlargement.

Angiotensin II enhances the increase in monocyte chemoattractant protein-1 production induced by tumor necrosis factor-α from 3T3-L1 preadipocytes

Monocyte chemoattractant protein-1 (MCP-1) and angiotensin II (Ang II) in adipose tissue are thought to induce systemic insulin resistance in rodents; but the precise mechanism is not fully clarified. We examined the mechanism of Ang II-induced and/or tumor necrosis factor-alpha (TNF-alpha)-induced MCP-1 production from 3T3-L1 preadipocytes. The MCP-1 protein and MCP-1 mRNA expression in 3T3-L1 preadipocytes were increased significantly by stimulation with TNF-alpha. We found no significant increase in MCP-1 concentrations by Ang II alone; but it enhanced the TNF-alpha-induced MCP-1 mRNA expression in a dose-dependent manner. Then, we examined the effect of Ang II and/or TNF-alpha on phosphorylation of extracellular signal-regulated kinase (ERK), p38MAPK, and IkappaB-alpha. Ang II and TNF-alpha clearly enhanced ERK and p38MAPK phosphorylation. IkappaB-alpha phosphorylation was enhanced by TNF-alpha, but not by Ang II. The MCP-1 mRNA expression induced by TNF-alpha and co-stimulation with Ang II was inhibited by either ERK inhibitor, p38MAPK inhibitor or NF-kappaB inhibitor. Moreover, Ang II enhanced the activation of AP-1 (c-fos) induced by TNF-alpha. Our results suggest that Ang II may serve as an additional stimulus on the TNF-alpha-induced MCP-1 production through the ERK-and p38MAPK-dependent pathways probably due to AP-1 activation.

Interstitial concentrations of adipokines in subcutaneous abdominal and femoral adipose tissue

Adipokines play important regulatory roles in the pathophysiology of obesity and insulin resistance. We measured plasma and interstitial concentrations of the adipokines adiponectin, resistin, leptin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) in subcutaneous, abdominal and femoral adipose tissue using calibrated, large-pore microdialysis technique in 8 healthy, lean men on 2 experimental days. The interstitial leptin concentration was 2.5-fold higher in subcutaneous, femoral than abdominal adipose tissue ( P < 0.05), but no regional differences were found for the remaining adipokines ( P > 0.05). Adiponectin and leptin concentrations were higher in plasma than subcutaneous adipose tissue (∼ 25-fold and ∼ 2-fold, respectively, P < 0.05), whereas MCP-1, IL-6 and IL-8 concentrations were higher in subcutaneous adipose tissue than plasma (∼ 100-fold, ∼ 200-fold and ∼ 1000-fold, respectively, P < 0.05). Resistin concentrations did not differ significantly between compartments. Adipose tissue blood flow (ATBF) showed no regional difference ( P > 0.05). The intra- and inter-subject variations of all investigated adipokines as well as of ATBF were substantial (coefficient of variation: 4–177%). In conclusion, interstitial leptin concentrations are ~ 2.5-fold higher in subcutaneous, femoral than abdominal adipose tissue, which might be a potential mechanism behind the health-benefits of “pear-shape”. Furthermore, subcutaneous adipose tissue has a marked production of pro-inflammatory adipokines.

Atherogenic Diet Promotes Atherosclerotic Lesion Formation by Enhancing Inflammatory Response in the LDL Receptor Null Mouse

The effect of an atherogenic diet on inflammatory response in elicited peritoneal macrophages and livers in relation to aortic lesion formation was assessed in LDL receptor null (LDLr‐/‐) mice. Mice were fed an atherogenic (20% fat, 0.2% cholesterol, w/w) or control (4% fat, 0.02% cholesterol, w/w) diet for 32 weeks. The atherogenic diet, relative to the control diet, resulted in significantly higher plasma concentrations of monocyte chemoattractant protein‐1 (MCP‐1, P&lt;0.01), tumor necrosis factor alpha (TNF‐alpha, P&lt;0.01) and interleukin‐6 (IL‐6, P&lt;0.001), more aortic wall macrophage deposition, and greater accumulation of both aortic free cholesterol (4.9‐fold, P&lt;0.001) and esterified cholesterol (6.4‐fold, P&lt;0.001). Elicited peritoneal macrophages isolated from the atherogenic diet, relative to the control diet, fed mice accumulated more esterified cholesterol (P&lt;0.001), had higher mRNA levels (P&lt;0.05) and secretion (P&lt;0.01) of MCP‐1. The atherogenic diet, relative to the control diet, significantly increased the production of IL‐6 (P&lt;0.05) and TNF‐alpha (P&lt;0.05) from the livers. These data suggest that the atherogenic diet resulted in higher plasma inflammatory factor concentrations, higher elicited peritoneal macrophage secretion and liver production of inflammatory factors, which in turn were associated with greater aortic cholesterol accumulation.

The Relation of Genetic and Environmental Factors to Systemic Inflammatory Biomarker Concentrations

Environmental and genetic correlates of inflammatory marker variability are incompletely understood. In the family-based Framingham Heart Study, we investigated heritability and candidate gene associations of systemic inflammatory biomarkers. In offspring participants (n=3710), we examined 11 inflammatory biomarkers (CD40 ligand, C-reactive protein, intercellular adhesion molecule-1, interleukin-6, urinary isoprostanes, monocyte chemoattractant protein-1, myeloperoxidase, P-selectin, tumor necrosis factor-alpha, tumor necrosis factor receptor II, fibrinogen). Heritability and bivariate genetic and environmental correlations were assessed by Sequential Oligogenic Linkage Analysis routines in 1012 family members. We examined 1943 tagging single-nucleotide polymorphisms in 233 inflammatory pathway genes with >or=5 minor allele carriers using a general genetic linear model. Clinical correlates explained 2.4% (CD40 ligand) to 28.5% (C-reactive protein) of the variability in inflammatory biomarkers. Estimated heritability ranged from 10.9% (isoprostanes) to 44.8% (P-selectin). Most correlations between biomarkers were weak although statistically significant. A total of 45 single-nucleotide polymorphism-biomarker associations met the q-value threshold of 0.25. Novel top single-nucleotide polymorphisms were observed in ICAM1 gene in relation to intercellular adhesion molecule-1 concentrations (rs1799969, P=1.32 x 10(-8)) and MPO in relation to myeloperoxidase (rs28730837, P=1.9 x 10(-5)). Lowest P values for trans-acting single-nucleotide polymorphisms were observed for APCS with monocyte chemoattractant protein-1 concentrations (rs1374486, P=1.01 x 10(-7)) and confirmed for IL6R with interleukin-6 concentrations (rs8192284, P=3.36 x 10(-5)). Novel potential candidates (APCS, MPO) need to be replicated. Our community-based data support the relevance of clinical and genetic factors for explaining variation in inflammatory biomarker traits.

Monocyte and Neutrophil Chemotactic Activity at the Site of Interstitial Inflammation in Patients on High-Flux Hemodialysis or Hemodiafiltration

Background/Aims: We have observed a difference between patients on low-flux hemodialysis (HD) or peritoneal dialysis and patients on hemodiafiltration (HDF) or high-flux HD in the capacity of transmigrated leukocytes to mobilize CD11b in response to inflammatory stimuli compared with healthy subjects. This could be due to different interstitial chemokine concentrations. Methods: We measured concentrations of circulating and interstitial macrophage inflammatory protein-1α (MIP-1α), matrix metalloproteinase-9 (MMP-9)/neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in 10 patients on HDF or high-flux HD and 11 healthy subjects by using immunoassay. Results: The interstitial concentrations of MIP-1α, MMP-9/NGAL and IL-8 were similar in patients and healthy subjects, while the corresponding concentration of MCP-1 was significantly higher in patients on HDF or high-flux HD as compared with healthy subjects (p < 0.01). Conclusion: We suggest that an equal or higher concentration of chemokines in the interstitium in patients with HDF or high-flux HD might be one mechanism responsible for the preserved function of transmigrated leukocytes.

Gingival crevicular fluid levels of monocyte chemoattractant protein-1 in periodontal health and disease

Objectives Monocyte chemoattractant protein-1 (MCP-1) stimulates the chemotaxis of monocytes and also several cellular events associated with chemotaxis thus causes recruitment of inflammatory cells. Its increased gingival crevicular fluid (GCF) levels in periodontal disease have been reported in previous studies. The present study has been carried out to assess the role of MCP-1 in periodontal disease progression and also to determine the effect of periodontal treatment on MCP-1 concentration in GCF. Design A total of 60 subjects were divided into three groups ( n = 20) based on gingival index (GI), probing pocket depth (PPD) and clinical attachment loss (CAL): healthy (group I), gingivitis (group II) and chronic periodontitis (group III). A fourth group (group IV) consisted of 20 subjects from group III, 6–8 weeks after treatment (i.e. scaling and root planing). GCF samples collected from each patient were quantified for MCP-1 using ELISA. Results The mean MCP-1 concentration in GCF was found to be the highest in group III, i.e. 72.60 pg/μl. The mean MCP-1 concentration in group I was 19.70 pg/μl and in group IV was 8.50 pg/μl. The mean MCP-1 concentration (37.00 pg/μl) in group II was found to lie in between the concentrations obtained in groups I and III. Conclusions GCF MCP-1 levels increased progressively with the progression of disease and decreased after treatment. Levels of MCP-1 correlated positively with clinical parameters like GI, PPD and CAL thus it can be considered as an inflammatory biomarker in periodontal disease and also deserves further consideration as a therapeutic target.

Increased circulating levels of matrix metalloproteinase (MMP)-8, MMP-9, and pro-inflammatory markers in patients with metabolic syndrome

Background Metabolic syndrome (MetS) predisposes to cardiovascular complications. Increased concentrations of pro-inflammatory mediators and imbalanced concentrations of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may reflect the pathophysiology of MetS. We compared the circulating levels of MMPs, TIMPs, and inflammatory mediators in MetS patients with those found in healthy controls. Methods We studied 25 healthy subjects and 25 MetS patients. The plasma levels of pro-MMP-2 and pro-MMP-9 were determined by gelatin zymography. The plasma concentrations of MMP-8, MMP-3, TIMP-1, TIMP-2, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule (sICAM-1), and sP-selectin were measured by ELISA kits. Results We found higher sP-selectin, sICAM-1, MCP-1, and IL-6 (all P < 0.05) concentrations in MetS patients compared with healthy controls. No differences in pro-MMP-2, MMP-3, and TIMP-2 levels were found (all P > 0.05). However, we found higher pro-MMP-9, MMP-8, and TIMP-1 levels in MetS patients compared with healthy controls (all P < 0.05). Conclusions Patients with MetS have increased circulating concentrations of pro-MMP-9, MMP-8, and TIMP-1 that are associated with increased concentrations of pro-inflammatory mediators and adhesion molecules. These findings suggest that MMPs may have a role in the increased cardiovascular risk of MetS patients. Pharmacological interventions targeting MMPs, especially MMP-9 and MMP-8 deserve further investigation in MetS patients.

Circulating concentrations of monocyte chemoattractant protein-1 are associated with menopause status in Korean women

Background Monocyte chemoattractant protein-1 (MCP-1) plays a role in adipose tissue inflammation and insulin resistance. Human circulating MCP-1 concentrations reportedly increase or remain unchanged according to obesity or insulin resistance in various ethnic populations; whether or not circulating MCP-1 concentrations increase after menopause has remained unclear. Methods We investigated the relationship between circulating MCP-1 concentrations and obesity or insulin resistance, and the relationship between circulating MCP-1 and menopause status in premenopausal ( n = 111) and postmenopausal ( n = 64) Korean women. Results Circulating MCP-1 concentrations were significantly higher in postmenopausal women than in obesity-matched premenopausal women; they did not differ between non-obese and obese subgroups of pre- and postmenopausal women. Circulating MCP-1 concentrations had a relationship with menopause status ( ρ = 0.500, p = 0.000), irrespective of obesity, but no relationship with obesity or insulin resistance. Circulating MCP-1 concentrations correlated with serum triglycerides ( r = 0.4, p = 0.001) and also correlated with serum triglyceride concentrations, after adjusting for age and obesity, in postmenopausal women. Conclusions Circulating MCP-1 concentrations are associated with menopause status itself, irrespective of obesity; they do not correlate with obesity or insulin resistance in Korean women, most of whom are not severely obese.

Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease.

BackgroundParaoxonase-1 (PON1) is an antioxidant enzyme synthesized by the liver. It protects against liver impairment and attenuates the production of the pro-inflammatory monocyte chemoattractant protein-1 (MCP-1). We investigated the relationships between hepatic PON1 and MCP-1 expression in rats with liver disease and explored the possible molecular mechanisms involved.MethodsCCl4 was administered for up to 12 weeks to induce liver damage. Serum and hepatic levels of PON1 and MCP-1, their gene and protein expression, nuclear transcription factors, and histological and biochemical markers of liver impairment were measured.ResultsHigh levels of PON1 and MCP-1 expression were observed at 12th week in the hepatocytes surrounding the fibrous septa and inflammatory areas. CCl4-administered rats had an increased hepatic PON1 concentration that was related to decreased gene transcription and inhibited protein degradation. Decreased PON1 gene transcription was associated with PPARδ expression. These changes were accompanied by increased hepatic MCP-1 concentration and gene expression. There were significant direct relationships between hepatic PON1 and MCP-1 concentrations (P = 0.005) and between PON1 and the amount of activated stellate cells (P = 0.001).ConclusionOur results from this experimental model suggest a hepato-protective role for PON1 against inflammation, fibrosis and liver disease mediated by MCP-1.

MCP-1 and MIP3-alpha serum levels in acute liver failure and molecular adsorbent recirculating system (MARS) treatment: A pilot study

Objective. The CC chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-3 alpha (MIP3-alpha) may be involved in the pathogenesis of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). In ALF and ACLF, the molecular adsorbent recirculating system (MARS) has been used to support liver function. Enhancement of MCP-1, as seen in other extracorporeal support systems such as haemodialysis, might thus have mitigated the beneficial effects of the MARS system in acute hepatic failure. Material and methods. Serum concentrations of MCP-1 and MIP3-alpha were measured in 10 patients with ALF or ACLF treated with MARS. Thirteen patients suffering from chronic hepatic failure (CHF) and 15 healthy individuals served as controls. Results. Baseline MCP-1 serum concentrations were significantly increased in ALF and ACLF patients as compared to patients with CHF (p=0.0027 and p=0.0046, respectively) and controls (p=0.0006 and p=0.0012, respectively). MIP3-alpha serum concentrations were also significantly enhanced in the ALF and ACLF groups as compared with those in CHF patients (p=0.0002 and p=0.0003, respectively) and controls (p<0.0001 and p<0.0001, respectively). Moreover, MIP3-alpha levels were significantly increased in CHF patients as compared to controls (p=0.0002). MCP-1 and MIP3-alpha concentrations did not change significantly during MARS treatment in ALF and ACLF patients. Conclusions. The CC chemokines MCP-1 and MIP3-alpha are increased in ALF and ACLF patients. MARS had no effect on MCP-1 and MIP3-alpha serum concentrations in patients with ALF and ACLF, and yielded no evidence of any harmful effects of the increase of these potentially hepatocidal chemokines.

Effect of nicotinamide on early graft failure following intraportal islet transplantation

Intraportal islet transplantation (IPIT) may potentially cure Type 1 diabetes mellitus; however, graft failure in the early post-transplantation period presents a major obstacle. In this study, we tested the ability of nicotinamide to prevent early islet destruction in a syngeneic mouse model. Mice (C57BL/6) with chemically-induced diabetes received intraportal transplants of syngeneic islet tissue in various doses. Islets were cultured for 24 h in medium with or without 10 mM nicotinamide supplementation. Following IPIT, islet function was confirmed by an intraperitoneal glucose tolerance test (IPGTT) and hepatectomy. The effects of nicotinamide were evaluated by blood glucose concentration, serum monocyte chemoattractant protein-1 (MCP-1) concentration, and immunohistology at 3 h and 24 h after IPIT. Among the various islet doses, an infusion of 300 syngeneic islets treated with nicotinamide exhibited the greatest differences in glucose tolerance between recipients of treated and untreated (i.e., control) islets. One day after 300 islet equivalent (IEQ) transplantation, islets treated with nicotinamide were better granulated than the untreated islets (P=0.01), and the recipients displayed a slight decrease in serum MCP-1 concentration, as compared to controls. After 15 days, recipients of nicotinamide-pretreated islets showed higher levels of graft function (as measured by IPGTT) than controls. The pretreatment also prolonged graft survival (>100 days) and function; these were confirmed by partial hepatectomy, which led to the recurrence of diabetes. Pretreatment of islet grafts with nicotinamide may prevent their deterioration on the early period following IPIT in a syngeneic mouse model.

Relation of Endothelial Dysfunction and Adipokines Levels to Insulin Resistance in Metabolic Syndrome Patients

Relation of Endothelial Dysfunction and Adipokines Levels to Insulin Resistance in Metabolic Syndrome Patients Obese metabolic syndrome (MS) patients were categorised into three groups: 44 with type 2 diabetes mellitus (T2DM)(D); 20 with T2DM and coronary artery disease (CAD) (DC), and 26 with MS alone (M). Eighteen healthy subjects were selected as controls (C). Insulin resistance (IR) was assessed by HOMA-IR. Adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) concentrations were measured by xMAP technology. Endothelin-1 (ET-1) was determined by ELISA. We used laser Doppler imaging for evaluating cutaneous endothelium-dependent vasodilatation in the hand. D and DC groups had significantly elevated IR compared with M or C group (P &lt; 0.01). TNF-α, IL-6, IL-8, MCP-1 and ET-1 levels in DC were significantly elevated compared with other groups (P &lt; 0.001). IL-6, IL-8, MCP-1 and ET-1 in D group were higher than those in C group (P &lt; 0.05). TNF-α, IL-6, IL-8, MCP-1 and ET-1 concentrations were correlated with HOMA-IR indexes and adiponectin levels. All patients had lower adiponectin concentrations than controls (P &lt; 0.001), but there were no differences between the patient groups. Only D and DC groups demonstrated a significant and similar decrease in LDI-Ach marker compared to C group (P &lt; 0.001). LDI-Ach values were significantly correlated with HOMA-IR indexes and adiponectin levels (P &lt; 0.001). Our findings show that obese MS patients have significantly increased HOMA-IR, TNF-α, IL-6, MCP-1 and IL-8 levels, decreased adiponectin concentration, and endothelial dysfunction, but the presence of T2DM and CAD in these patients is associated with more pronounced endothelial dysfunction and increased production of inflammatory cytokines and chemokines.

Serum Monocyte Chemoattractant Protein-1 Concentrations Associate With Diabetes Status but Not Arterial Stiffness in Children With Type 1 Diabetes

OBJECTIVEThe relationship between circulating markers of inflammation and arterial stiffness in children with type 1 diabetes is not well studied. We tested whether inflammatory monocyte chemoattractant protein (MCP)-1 concentrations correlate with arterial stiffness or type 1 diabetes status.RESEARCH DESIGN AND METHODSMCP-1 concentrations and radial tonometry data were available for 98 children with type 1 diabetes and 55 healthy control subjects. Arterial stiffness was calculated as augmentation index corrected for a heart rate of 75 (AI75). Correlation between MCP-1 and AI75 and differences in MCP-1 concentrations between case and control subjects were tested.RESULTSMCP-1 was significantly higher in children with type 1 diabetes than in control subjects (P < 0.001). However, there were no correlations between MCP-1 and AI75 in the overall sample or upon stratification by type 1 diabetes status (range P = 0.28–0.66).CONCLUSIONSCirculating MCP-1 was not associated with arterial stiffness but was significantly elevated in children with type 1 diabetes, indicating a proinflammatory state in children as young as 10 years. The clinical significance of MCP-1 elevation in type 1 diabetes needs further investigation.

Role of CC Chemokine Receptor 2 in Bone Marrow Cells in the Recruitment of Macrophages into Obese Adipose Tissue

The MCP-1 (monocyte chemoattractant protein-1)/CCR2 (CC motif chemokine receptor-2) pathway may play a role in macrophage infiltration into obese adipose tissue. Here we investigated the role of CCR2 in the recruitment of bone marrow-derived macrophages into obese adipose tissue in vitro and in vivo. Using the TAXIScan device, which can measure quantitatively the directionality and velocity of cell migration at time lapse intervals in vitro, we demonstrated that bone marrow cells (BMCs) from wild type mice migrate directly toward MCP-1 or culture medium conditioned by adipose tissue explants of genetically obese ob/ob mice, which are efficiently suppressed by pharmacological blockade of CCR2 signaling. The number of F4/80-positive macrophages was reduced in the adipose tissue from high fat diet-fed obese KKAy or ob/ob mice treated with a CCR2 antagonist propagermanium relative to vehicle-treated groups. We also found that the number of macrophages is reduced in the adipose tissue from ob/ob mice reconstituted with CCR2(-/-) BMCs (ob/ob + CCR2(-/-) BMCs) relative to those with CCR2+/+ BMCs (ob/ob + CCR2+/+ BMCs). Expression of mRNAs for CD11c and TLR4 (Toll-like receptor 4) markers of proinflammatory M1 macrophages was also decreased in the adipose tissue from ob/ob + CCR2(-/-) BMCs relative to ob/ob + CCR2+/+ BMCs, whereas mannose receptor and CD163, markers of anti-inflammatory M2 macrophages, were unchanged. This study provides in vivo and in vitro evidence that CCR2 in bone marrow cells plays an important role in the recruitment of macrophages into obese adipose tissue.

Differential Recruitment of Dendritic Cells and Monocytes to Respiratory Mucosal Sites in Children with Influenza Virus or Respiratory Syncytial Virus Infection

Influenza virus and respiratory syncytial virus (RSV) are among the most common viruses causing infections of the lower respiratory tract in young children. Although there are important differences in the immunopathogenesis of these 2 viral pathogens, little is known about how they affect antigen-presenting cells in children with acute infections. To characterize the immune cells that are mobilized to the respiratory tract by influenza virus and RSV, we analyzed nasal wash and blood samples obtained from children hospitalized with acute respiratory infections. Influenza virus and RSV mobilize immune cells, including myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), to the nasal mucosa. Patients with influenza virus infection had greater numbers of mDCs, pDCs, and monocytes in nasal wash samples than did patients with RSV infection. The frequencies of respiratory tract and blood T cell subsets were not affected by infection with influenza virus or RSV. Monocyte chemoattractant protein-1 concentrations in nasal wash samples were significantly increased in patients with influenza virus infection but not in those with RSV infection. RANTES (regulated on activation, normally T cell expressed and secreted) concentrations were increased only in the blood of patients with influenza virus infection. Infection with influenza virus or RSV mobilizes antigen-presenting cells to the respiratory tract. The differences in antigen-presenting cell numbers and cytokine concentrations suggest that there are distinctive, early immune responses to these 2 viruses.

US28 in melanoma growth

The human cytomegalovirus (hCMV) encodes the G protein-coupled receptor (vGPCR) US28. This receptor signals constitutively and interacts with a broad range of chemokines, which are crucial to the pathophysiological significance and immunoregulatory aspects of this receptor. Chemokines and their receptors have been shown to be key determinants of tumor growth and formation of metastases. US28 exerts anti-tumorigenic effects in two melanoma cell lines. Here we show that in contrast to all other previously studied cell lines, US28 is expressed on the cell surface in the melanoma cell lines Sbcl2 and 451Lu. We found that GASP – the G protein-coupled receptor-associated sorting protein – which sorts US28 and many other GPCRs to the lysosomes is absent in melanoma cells. The absence of GASP might affect the tumor-suppressing properties of US28. Melanoma cells produce several chemokines, one of them is the monocyte chemoattractant protein-1 (MCP-1). We found that the MCP-1 level in the supernatants of 451Lu cells increased when US28 wt was expressed. US28Δ317, a truncated mutant of US28 which is known to have enhanced signalling capacity compared to US28 wt, increased the MCP-1 concentration up to 20-fold. We speculate that the constitutive signalling of the receptor regulates the MCP-1 production of melanoma cells.