Higher Levels Of Monocyte Chemotactic Protein-1 Research Articles

Analysis of Biomarkers and Marginal Bone Loss in Platform-Switched and Nonplatform-Switched Implants: A Randomized Clinical Trial.

Objectives To compare the peri-implant crevicular fluid (PICF) biomarker levels, peri-implant status, and marginal bone level (MBL) differences of implants restored with randomly assigned nonplatform-switched (NPS) or platform-switched (PS) abutments. Methods Ninety-four implants in 27 subjects were included in this study. Receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) levels in PICF, peri-implant health, and the change in the MBL were evaluated at the time of restoration (T1) and after 12 months (T2). Results The IL-1β levels decreased and the RANKL, OPG, and MCP-1 levels increased from T1 to T2 (P < 0.05) in both groups. RANKL/OPG ratio at T1, MCP-1 levels at T2, and the MCP-1 change from T1 to T2 were lower in the PS group than in the NPS group (P < 0.05). MBL change was lower (0.51 ± 0.31 mm) in the PS group than that (0.75 ± 0.29 mm) in the NPS group at T2 (P < 0.001). Peri-implant health status between the study groups was negligible. Conclusion PS was superior to NPS regarding the preservation of MBL. Higher MCP-1 levels, altered RANKL/OPG ratio, and lower OPG levels in the NPS group could be associated with subclinical peri-implant bone remodeling.

Prediction of anti‐VEGF efficacy in diabetic macular oedema using intraocular cytokines and macular optical coherence tomography

In eyes with diabetic macular oedema (DME), aqueous humour (AH) cytokine levels before and after anti-vascular endothelial growth factor (VEGF) treatment were compared and correlated with optical coherence tomography structural parameters. This prospective study included 56 control patients with cataracts and 83 patients with DME manifesting as diffuse retinal thickening (DRT), cystoid macular oedema and serous retinal detachment (SRD). AH samples were obtained before intravitreal injection of anti-VEGF or cataract surgery. VEGF, interleukin (IL)-6, IL-8, IL-10, interferon-inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) levels were measured by multiplex bead assay. AH cytokine levels, central macular thickness (CMT), number of hyper-reflective foci (HF), continuity of external limiting membrane and ellipsoid zone (EZ) and best-corrected visual acuity were evaluated. In SRD, IL-6 and MCP-1 levels and HF were increased (all p < 0.05) compared to DRT. At baseline, the number of HF was correlated with VEGF, IL-6, IL-8, IP-10 and MCP-1 (all p < 0.05). Eyes sensitive to anti-VEGF treatment had high baseline levels of VEGF, MCP-1, HF and many EZ disruptions (all p < 0.05). DME patients with normal VEGF levels but with high levels of IL-8, IP-10 and MCP-1 (all p < 0.05) had little change in CMT after anti-VEGF treatment (p = 0.678). AH concentrations of some inflammatory cytokines in DME were differentially expressed among the three DME morphologies. HF was associated with VEGF and other inflammatory cytokine levels. Multiple HF at baseline predicted a significant decrease in CMT, and eyes with normal VEGF but increased inflammatory cytokines may be insensitive to anti-VEGF treatment.

MCP-1, KC-like and IL-8 as critical mediators of pathogenesis caused by Babesia canis.

Canine babesiosis caused by the intraerythrocytic protozoan parasite Babesia canis is a tick-borne disease characterized by a host response that involves both cellular and humoral immunity. This study focuses on the secretion of cytokines Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Keratinocyte Chemotactic-like (KC-like), Interleukins (IL)-2, IL-7, IL-8, IL-10, IL-15, IL-18 and Monocyte Chemotactic Protein-1 (MCP-1) in babesiosis caused by Babesia canis upon treatment with Imizol®. We assessed time dependent changes in cytokine levels and tested whether these changes correlate with pathogenesis of the disease. Sixteen healthy dogs and 31 dogs infected with Babesia canis, of which 18 showed complications, were treated with Imizol®. One dog died during the study (3.2%). Longitudinal study was perfomed by monitoring dogs at the first day of presentation (day 1) and 6 days later (day 7). Our results show that higher MCP-1 levels on day 1 are positively associated with the occurrence of complications, (complicated vs. uncomplicated; p = 0.00016). A similar pattern was observed for KC-like on day 1 (p = 0.0326) and day 7 (p = 0.044). Moreover, babesiosis caused by B. canis produced a steady increase in IL-8 levels with a moderate to strong negative correlation with erythrocyte counts and hematocrit in uncomplicated diseased dogs only (Spearman's rank correlation coefficient rs = -0.582 and rs = -0.598 respectively). Like for MCP-1, KC-like levels also differed in complicated and uncomplicated diseased dogs on day 1 (p = 0.03236) and day 7 (p = 0.044). Furthermore, KC-like levels were strongly correlated with IL-8 levels (rs = 0.663–0.7) and non-segmented neutrophil counts (rs = 0.572–0.732) in both diseased groups. Analysis of ROC suggests the use of serum levels of MCP-1 and IL-7 as predictors of the occurrence of complications with an AUC of 0.906 and 0.896 respectively and linear combinations of MCP-1, KC-Like, IL-7 and GM-CSF with values up to AUC = 0.983. Cytokine cluster analysis presented in this study can contribute to a better understanding of the pathogenesis of babesiosis and serve as a prognostic tool for the early detection of cases with highest likelihood of developing complications. Overall, our studies show that infection by B. canis elicits a cytokine pattern that is distinct from that observed with B. rossi, and that some of the inflammatory mediators can be useful to predict complications. Our results also suggest targets for the development of novel therapeutic strategies in babesiosis caused by B. canis.

Association of increased levels of MCP-1 and cathepsin-D in young onset type 2 diabetes patients (T2DM-Y) with severity of diabetic retinopathy

AimYoung onset type 2 diabetes patients (T2DM-Y) have been shown to possess an increased risk of developing microvascular complications particularly diabetic retinopathy. However, the molecular mechanisms are not clearly understood. In this study, we investigated the serum levels of monocyte chemotactic protein 1 (MCP-1) and cathepsin-D in patients with T2DM-Y without and with diabetic retinopathy. MethodsIn this case–control study, participants comprised individuals with normal glucose tolerance (NGT=40), patients with type 2 diabetes mellitus (T2DM=35), non-proliferative diabetic retinopathy (NPDR=35) and proliferative diabetic retinopathy (PDR=35). Clinical characterization of the study subjects was done by standard procedures and MCP-1 and cathepsin-D were measured by ELISA. ResultsCompared to control individuals, patients with T2DM-Y, NPDR and PDR exhibited significantly (p<0.001) higher levels of MCP-1. Cathepsin-D levels were also significantly (p<0.001) higher in patients with T2DM-Y without and with diabetic retinopathy. Correlation analysis revealed a positive association (p<0.001) between MCP-1 and cathepsin-D levels. There was also a significant negative correlation of MCP1/cathepsin-D with C-peptide levels. The association of increased levels of MCP-1/cathepsin-D in patients with DR persisted even after adjusting for all the confounding factors. ConclusionAs both MCP-1 and cathepsin-D are molecular signatures of cellular senescence, we suggest that these biomarkers might be useful to predict the development of retinopathy in T2DM-Y patients.

Effect of On-Pump CABG (Roller Versus Centrifugal Systems) on MCP-1, TNFsR and IL6 Behaviour

Background We aimed to evaluate the cytokines monocyte chemotactic protein 1 (MCP-1), TNF soluble receptor (TNF-sR1) and interleukin 6 (IL-6) behavior in patients submitted to CABG (coronary artery bypass grafting) surgeries comparing roller to centrifugal extracorporeal circulation (ECC) pumping systems. Methods We randomized prospectively 43 adults who had elective on-pump CABG with the use of a roller (group I; n = 22) or a centrifugal system (group II; n = 21). Plasma levels of MCP-1, TNF-sR1 and IL-6 were determined by Elisa before the induction of anaesthesia (T1), 35 min after initiation of ECC (T2), 1 min after aortic declamping (T3), and 2, 6 and 24 h after the operation (T4, T5 and T6, respectively). The two groups were matched according to preoperative features. The groups I and II showed similar perioperative characteristics and clinical postoperative outcomes. The plasma levels of MCP-1 and TNF-sR1 reached a peak at T4 and T5 in both groups. MCP-1 in group I was significantly higher (P = 0.020) than in group II at T5, while plasma levels of TNF-sR1 in group I were significantly (P = 0.028) higher than in group II at T4. In both groups, the levels of IL-6 reached a peak at T5. Group I showed higher IL-6 plasma levels (P = 0.006). Conclusion We conclude that both roller and centrifugal pumps induce inflammatory responses to on-pump CABG procedures but higher levels of MCP-1, TNF-sR and IL6 were verified using roller systems.

MCP/CCR2 signaling is essential for recruitment of mesenchymal progenitor cells during the early phase of fracture healing.

ObjectiveThe purpose of this study was to investigate chemokine profiles and their functional roles in the early phase of fracture healing in mouse models.MethodsThe expression profiles of chemokines were examined during fracture healing in wild-type (WT) mice using a polymerase chain reaction array and histological staining. The functional effect of monocyte chemotactic protein-1 (MCP-1) on primary mouse bone marrow stromal cells (mBMSCs) was evaluated using an in vitro migration assay. MCP-1−/− and C-C chemokine receptor 2 (CCR2)−/− mice were fractured and evaluated by histological staining and micro-computed tomography (micro-CT). RS102895, an antagonist of CCR2, was continuously administered in WT mice before or after rib fracture and evaluated by histological staining and micro-CT. Bone graft exchange models were created in WT and MCP-1−/− mice and were evaluated by histological staining and micro-CT.Results MCP-1 and MCP-3 expression in the early phase of fracture healing were up-regulated, and high levels of MCP-1 and MCP-3 protein expression observed in the periosteum and endosteum in the same period. MCP-1, but not MCP-3, increased migration of mBMSCs in a dose-dependent manner. Fracture healing in MCP-1−/− and CCR2−/− mice was delayed compared with WT mice on day 21. Administration of RS102895 in the early, but not in the late phase, caused delayed fracture healing. Transplantation of WT-derived graft into host MCP-1−/− mice significantly increased new bone formation in the bone graft exchange models. Furthermore, marked induction of MCP-1 expression in the periosteum and endosteum was observed around the WT-derived graft in the host MCP-1−/− mouse. Conversely, transplantation of MCP-1−/− mouse-derived grafts into host WT mice markedly decreased new bone formation.ConclusionsMCP-1/CCR2 signaling in the periosteum and endosteum is essential for the recruitment of mesenchymal progenitor cells in the early phase of fracture healing.

Serum Levels of TGF-β1 and MCP-1 as Biomarkers for Progressive Coal Workers’ Pneumoconiosis in Retired Coal Workers: A Three-year Follow-up Study

Various cytokines activated by the inhalation of coal dust may mediate inflammation and lead to tissue damage. Objective of this study was to examine the relationships between coal workers’ pneumoconiosis (CWP) progression over a 3 yr period and the serum levels of cytokines in 85 retired coal workers. To investigate the relevance of serum cytokines in CWP, serum levels of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), transforming growth factor–beta1 (TGF-β1), and monocyte chemotactic protein-1 (MCP-1) as progressive CWP biomarkers were studied in relation to the progression of pneumoconiosis over a 3 yr period in 85 patients with CWP. CWP progression was evaluated through paired comparisons of chest radiographs. Median levels of TGF-β1 and MCP-1 were significantly higher in subjects with progressive CWP than in those without CWP progression. The area under the ROC curve for TGF-β1 (0.693) and MCP-1 (0.653) indicated that these cytokines could serve as biomarkers for the progression of CWP. Serum TGF-β1 levels were related to the progression of CWP (β=0.247, p=0.016). The results suggest that high serum levels of TGF-β1 and MCP-1 are associated with the progression of CWP.

Serum levels of TGF-β1 and MCP-1 as biomarkers for progressive coal workers' pneumoconiosis in retired coal workers: a three-year follow-up study.

Various cytokines activated by the inhalation of coal dust may mediate inflammation and lead to tissue damage. Objective of this study was to examine the relationships between coal workers' pneumoconiosis (CWP) progression over a 3 yr period and the serum levels of cytokines in 85 retired coal workers. To investigate the relevance of serum cytokines in CWP, serum levels of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-β1), and monocyte chemotactic protein-1 (MCP-1) as progressive CWP biomarkers were studied in relation to the progression of pneumoconiosis over a 3 yr period in 85 patients with CWP. CWP progression was evaluated through paired comparisons of chest radiographs. Median levels of TGF-β1 and MCP-1 were significantly higher in subjects with progressive CWP than in those without CWP progression. The area under the ROC curve for TGF-β1 (0.693) and MCP-1 (0.653) indicated that these cytokines could serve as biomarkers for the progression of CWP. Serum TGF-β1 levels were related to the progression of CWP (β=0.247, p=0.016). The results suggest that high serum levels of TGF-β1 and MCP-1 are associated with the progression of CWP.

Monocyte chemotactic protein-1 (MCP-1) is the central mediator of inflammation in the ovarian follicle of obese women

To investigate serum, follicular fluid (FF) and granulosa cell (GC) inflammatory marker levels in normal, overweight and obese women undergoing ART. Prospective controlled study. 84 women (age:37±5) who underwent COH followed by oocyte retrieval were included. Serum was collected in early follicular phase of the IVF cycle. FF was collected only from the first follicle. Cumulus GCs from large follicles >14mm were isolated from oocytes. FF inflammatory marker levels (MCP-1, IL-1α, IL-1β, IL-2, Il-4, IL-6, IL-8, IL-10, EGF, GM-CSF, TGFα, TNFα, TNFβ, VEGF, Eotaxin, FGF2) were measured using Milliplex assay. Serum and FF levels of CRP, OxLDL,Catalase and IL-18 were measured using ELISA. mRNA was isolated from GCs, and gene expression of MCP-1, CCR2 (MCP-1 receptor), SRB, ATF, GPx and Lox1 was quantified using qRT-PCR. Statistical analyses: Pearson and Spearman rank correlation, Student t and Mann-Whitney U tests with signifance at 0.05. In FF only MCP-1 was significantly correlated with BMI (r=0.45, p=0.003), while in serum, Catalase and CRP were significantly correlated with BMI (r=0.4, p=0.04 and r=0.6 p=0.02). Obese women (BMI>=30; n=13) had higher MCP-1 levels in their FF than lean women (BMI<25, n=15) (821±403 vs 444±210 pg/ml, p=0.003). MCP-1 was also expressed in the GCs whereas CCR2 was not. While FF MCP-1 correlated with BMI, GC MCP-1 did not (p=0.85). Other inflammatory markers: SRB, ATF, GPx and Lox1 were also detected in GCs, but their levels did not correlate to BMI. MCP-1 is a marker of inflammation and chemotactic for macrophages. Our study shows MCP-1 to be the only inflammatory marker that is significantly increased in FF of obese women, suggesting a role for MCP-1 in obesity-induced ovarian dysfunction. However CCR2 was not detected in the GCs. These data suggest that GCs are not the target of MCP-1 but may contribute to MCP-1 production. Hence in the obese patient, MCP-1 may attract monocytes and lead to inflammation in the ovarian follicle.

Apolipoprotein E –/– mice have delayed skeletal muscle healing after hind limb ischemia–reperfusion

Classic studies of limb ischemia-reperfusion injury have been performed using young healthy mice. However, patients with peripheral vascular disease are older and often exhibit metabolic derangements that may delay healing after revascularization. Mice with genetic deletion of apolipoprotein E (ApoE(-/-)) have been used as a model in various experimental scenarios of hypercholesterolemia. These experiments evaluated the inflammatory response and changes in skeletal muscle morphology during the acute and chronic phases of limb ischemia-reperfusion injury in aged ApoE(-/-) mice. Age-matched ApoE(-/-) and wild-type (Wt) mice underwent 1.5 hours of unilateral hind limb ischemia, followed by 1, 7, or 14 days of reperfusion (DR). Histologic analysis of skeletal muscle fiber injury was assessed at 1DR. Morphologic evidence of muscular fiber maturation was assessed at 14DR. Levels of MyoD and myogenin, markers of skeletal muscle differentiation, were assessed at 7 and 14DR using Western blots. Markers of inflammation, including myeloperoxidase, macrophage inflammatory protein-2 (MIP-2), monocyte chemotactic protein-1 (MCP-1), and osteopontin, were assayed using enzyme-linked immunosorbent assay and chemokine (C-C motif) receptor 2 (CCR2) using Western blots at 1, 7, and 14DR. After 1DR, tissue adenosine 5'-triphosphate (ATP) levels were measured to assess metabolic activity. Unpaired t test and Mann-Whitney test were used for comparisons. Histologic evaluation of skeletal muscle after 1DR showed no difference in the degree of injury between Wt and ApoE(-/-) mice. However, at 14DR, ApoE(-/-) mice had higher percentage of immature muscle fibers than Wt mice. Myogenin level was lower in the ApoE(-/-) mice at 7DR. Injured skeletal muscle of ApoE(-/-) mice had lower levels of myeloperoxidase than Wt mice at 7 DR and higher levels of MCP-1 at 14DR. There was no difference in the levels of tissue ATP, MIP-2, osteopontin, or CCR2 at all experimental intervals. Although there was no difference between the injured muscle of Wt and ApoE(-/-) mice during the acute phase of reperfusion, ApoE(-/-) mice showed delay in skeletal muscle healing during the chronic phase of reperfusion. This lag in muscle regeneration was associated with lower levels of myogenin at 7DR and an increased level of MCP-1 at 14DR in the ApoE(-/-) mice. The delay in skeletal muscle healing in the ApoE(-/-) mice may have broader implications for poor tissue healing and functional recovery in elderly patients who have vascular risk factors such as hypercholesterolemia.

Monocyte Chemoattractant Protein 1, Active Carboxypeptidase B and CAPAP at Hospital Admission Are Predictive Markers for Severe Acute Pancreatitis

Background: CAPAP, the activation peptide of procarboxypeptidase B, is a predictor of severe acute pancreatitis (AP). Active carboxypeptidase (aCAP) may be a better predictor, as its turnover is slower. Monocyte chemotactic protein-1 (MCP-1) is an early inflammatory marker and increases before complications in severe AP. We conducted a cohort study to evaluate these markers as predictors for severe AP. Method: 140 patients with AP were included, retrospectively grouped as severe or mild by the Atlanta classification. CAPAP, MCP-1 and aCAP were analyzed in admission samples. Receiver operating characteristic curves determined high vs. low levels. Results: The levels of all markers were significantly higher in patients with severe disease. High levels of serum MCP-1 was associated with a high risk of developing severe AP (OR 40.8; 95% CI 8.5–195). High ORs were also seen for urine MCP-1 (OR 7.3; 95% CI 2.2-24.3), serum CAPAP (OR 5.4; 95% CI 1.6–17.7), urine CAPAP (OR 4.8; 95% CI 1.6–14.2), and serum aCAP (OR 3.7; 95% CI 1.2–11.3). Conclusion: Serum MCP-1 at admission was strongly associated with development of severe AP. MCP-1 in urine, CAPAP in serum and urine and aCAP may also be useful for predicting Severe AP.

The NF-κB and IκB System in Injured Arteries

Activation of endothelial cells and dedifferentiation of smooth muscle cells (SMC) are events in the development of vascular disease. The NF-κB transcription factor family and its inhibitory proteins (IκB) have been implicated in regulating the expression of genes associated with the concomitant inflammatory response. To determine the role of the NF-κB/IκB system in vivo, the present study used the balloon catheter injury model in the rat carotid artery. Immunoblotting revealed that higher levels of the NF-κB family members p50, p52, p65, c-Rel, and RelB were expressed in injured arteries during lesion formation compared to normal vessels. Using electromobility shift assays, low levels of constitutively activated NF-κB were seen in normal carotid arteries and an induction occurred during times of rapid SMC proliferation. Furthermore, immediately after injury, the levels of the inhibitor proteins IκBα, IκBβ, and p105 were dramatically reduced. Consistent with the activation of NF-κB, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) were induced in SMC and endothelial cells as early as 4 h after injury and this was accompanied by adhesion of monocytes/macrophages. SMC forming a pseudoendothelium in chronically denuded vessels continued to express high levels of VCAM-1 and MCP-1, thus perpetuating the inflammatory response. These findings link the activation of NF-κB to the inflammatory response and to intimal lesion formation following vascular injury.

Interferon γ induces differential upregulation of α and β chemokine secretion in colonic epithelial cell lines

Background—Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the α chemokine interleukin 8 (IL-8), a neutrophil...

Differential secretion of chemokines from peripheral blood in pregnant compared with non-pregnant women

The maintenance of a normal pregnancy is dependent on the delicate interaction between the endocrine and the immune systems. Cytokines are thought to play a key role in pregnancy by way of local modulation of the immune system at the level of peripheral leukocytes. This study examined the potential of peripheral venous blood cultures from pregnant women throughout gestation and from non-pregnant women to produce the chemokines monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8) and RANTES. Significantly ( P=<0.001), higher levels of MCP-1 were released from peripheral blood cultures from pregnant women at term than during the first trimester or from women who were not pregnant. This could not be accounted for by differences in differential blood counts. Significantly higher levels ( P=<0.05) of MCP-1 were released from PBMC preparations from pregnant compared with non-pregnant women. No `rebound' increase in MCP-1 was observed on withdrawing progesterone support to the PBMC preparations. MCP-1 was secreted predominately from CD14 + cells with those from pregnant women producing more than those from non-pregnant women. There was no statistical difference in release of IL-8 or RANTES from either peripheral blood or PBMC preparations from pregnant or non-pregnant women. IL-8 and RANTES were secreted from CD14 + and CD14 − cells, respectively. The hypothesis proposed is that the monocytes are fundamentally different in pregnancy and that measurement of MCP-1 has the potential to act as a marker of pregnancy status.

Selective elevation of monocyte chemotactic protein-1 in the cerebrospinal fluid of AIDS patients with cytomegalovirus encephalitis.

The CC chemokine monocyte chemotactic protein-1 (MCP-1) was markedly elevated in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-infected patients with cytomegalovirus (CMV) encephalitis. The MCP-1 CSF levels in CMV encephalitis were markedly higher than those in the CSF of HIV-infected patients with or without unrelated neurologic diseases, including progressive multifocal leukoencephalopathy, cryptococcal meningitis, toxoplasmic encephalitis, and primary lymphoma. Interleukin-8, RANTES, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta were not substantially increased in the CSF of CMV encephalitis patients. High levels of MCP-1 may underlie monocyte recruitment and tissue damage in CMV encephalitis and may represent a rapid and useful tool in the diagnostic armamentarium for neurologic disorders associated with HIV infection.