Macrophage Monocyte Chemoattractant Protein-1 Research Articles

The effect of barberry (Berberis vulgaris) consumption on flow-mediated dilation and inflammatory biomarkers in patients with hypertension: A randomized controlled trial.

Hypertension is considered as an important cardiovascular risk factor and evidence suggests that hypertension and endothelial dysfunction reinforce each other. Polyphenol-rich foods, such as barberry can reduce the risk of cardiovascular disease. Our aim was to investigate the effects of barberry consumption on vascular function and inflammatory markers in hypertensive subject. In this randomized controlled parallel trial, 84 hypertensive subjects of both genders (aged 54.06 ± 10.19 years; body mass index 28.02 ± 2.18 kg/m2 ) were randomly allocated to consume barberry (10 g/day dried barberry) or placebo for 8 weeks. Before and after the intervention, changes in brachial flow-mediated dilation (FMD) and plasma macrophage/monocyte chemo-attractant protein-1 (MCP-1), vascular cellular adhesion molecule-1, and intracellular adhesion molecule-1 (ICAM-1) were measured. An intention-to-treat analysis was performed. Compared to placebo (n = 42), barberry consumption (n = 42) improved FMD (B [95% CI] was 6.54% [4.39, 8.70]; p < .001) and decreased plasma ICAM-1 (B [95% CI] was -1.61 ng/ml [-2.74, -0.48]; p = .006). MCP-1 was significantly lower in the barberry group compared with the placebo group (B [95% CI] was -37.62 pg/ml [-72.07, -3.17]; p = .033). Our results indicate that barberry consumption improves FMD and has a beneficial effect on plasma ICAM-1 and MCP-1 in hypertensive patients. This trial was registered at the Iranian Registry of Clinical Trial (IRCT) with number IRCT20160702028742N8.

Local cyclical compression modulates macrophage function in situ and alleviates immobilization-induced muscle atrophy.

Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages in situ The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro Together with the LCC-induced movement of intramuscular interstitial fluid detected by µCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.

Evaluation of Cardioprotective Effects of Genistein against Diabetes-induced Cardiac Dysfunction in Rats

Purpose: To investigate the possible cardioprotective effects and potential pharmacological mechanism of genistein.Methods: Six-week old ZDF and lean rats were randomized into 4 groups (8 rats/group), including group 1 (control lean rats); group 2 (lean rats treated with genistein, 2.5 mg/kg); group 3 (control ZDF rats); and group 4 (ZDF treated with genistein). Two groups (2 and 4) were treated with genistein for 12 weeks, and cardiac functions and metabolic alterations were determined. Macrophage/monocyte chemo-attractant protein-1 (MCP-1), vascular cellular adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) secretion and their messenger RNA transcription level also were observed.Results: Genistein attenuated diabetes-induced cardiac dysfunction and pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signalling pathways. In addition, genistein treatment markedly reduced diabetic-induced MCP-1 (83.33 %), VCAM-1 (74.66 %) and ICAM-1 (71.42 %) secretion and mRNA transcription in ZDF rats.Conclusion: The results demonstrate the putative effects of genistein against cardiovascular dysfunction by improving glucose homeostasis, attenuating oxidative stress and reduced diabeticinduced endothelial dysfunction in ZDF rats. Thus, genistein is a potential candidate for the prevention of cardiovascular diseases.Keywords: Cardiac dysfunction, Genistein, Oxidative stress, Inflammatory response, Insulin resistance, Glucose tolerance

Anti‐Atherogenic Effects of Lesion‐Targeted Epigallocatechin Gallate (EGCG) ‐ Loaded Nanoparticles

ObjectivesMacrophages are determinant cells for atherosclerotic lesion formation. The objectives of this study were to incorporate macrophage target ligands on the surface of biocompatible and biodegradable epigallocatechin gallate (EGCG)‐loaded nanoparticles (Enano), to evaluate their target specificity to macrophages and anti‐atherogenic effects in vitro and in vivo.MethodThe target specificity to macrophages (in vitro) and to atherosclerotic lesions in low density lipoprotein receptor knockout (LDLr‐/‐) mice was measured using a fluorescence microscopy and IVIS® in vivo imaging system, respectively. Macrophage cholesterol content was determined using a HPLC method, and macrophage monocyte chemoattractant protein 1 (MCP‐1) release was measured using an ELISA kit. After treating LDLr‐/‐ mice with EGCG, untargeted Enano, targeted Enano, void untargeted nano, void targeted nano, or saline via weekly intravenous injection for 20 weeks, atherosclerotic lesion area and inflammatory response were determined.ResultsAs compared to untargeted Enano, targeted Enano significantly increased their binding affinity to THP‐1 macrophages, increased macrophage EGCG content and decreased macrophage cholesterol content and macrophage release of MCP‐1imageThe targeted Enano improved the target specificity to atherosclerotic lesions, and decreased atherosclerotic lesion area and inflammatory response in LDLr‐/‐ miceimageConclusionsTargeted nanoparticles represent a potential breakthrough in molecular imaging of atherosclerosis and have a potential for the prevention and treatment of atherosclerosis.

Genistein Inhibits ox-LDL-induced VCAM-1, ICAM-1 and MCP-1 Expression of HUVECs Through Heme Oxygenase-1

Genistein, a principal component of soybean isoflavones, plays an important role in the prevention of atherosclerosis. However, the detailed mechanisms have not been fully investigated. The aims of this study were to evaluate the anti-atherosclerotic effect and investigate potential pharmacological mechanism of genistein. A model of oxidized low-density lipoprotein (ox-LDL)-induced injury in on human umbilical vein endothelial cells (HUVECs) was established to evaluate the protective role of genistein. Macrophage/monocyte chemoattractant protein-1 (MCP-1), vascular cellular adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) secretion and their messenger RNA transcription were observed via enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase PCR (RT-PCR). Meanwhile, the study investigated the role of Nrf2/HO-1 pathway during the process. Pretreatment with genistein markedly reduced ox-LDL-induced MCP-1, VCAM-1 and ICAM-1 secretion and mRNA transcription, which was further decreased by the inducer of HO and reversed by the inhibitor of HO; additionally, the effects were accompanied with upregulating HO-1 mRNA and protein expression and markedly abolished with Nrf2 siRNA. Anti-inflammatory effect of genistein on endothelial cells may be associated with the activation of Nrf2/HO-1 pathway.

Tubular cell-Escherichia coli interaction products modulate migration of monocytes through generation of transforming growth factor-beta and macrophage-monocyte chemoattractant protein-1.

Urinary tract infection is a common occurrence often associated with renal interstitial inflammation in the form of accumulation of mononuclear cells. We hypothesized that bacteria activate tubular cells to secrete cytokines, which may promote migration of mononuclear cells at the site of interaction. We evaluated the migration of monocytes in response to tubular cell products (TC-S) and interaction products of E. coli with proximal tubular cells (TC-EC-S; concentrations of 5%, 10%, and 25%) using a modified Boyden chamber. To determine the molecular mechanism, we evaluated the effect of antibodies against macrophage-monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta (TGF-beta) on E. coli-tubular cell interaction product-induced migration of monocytes. In addition, we studied the effect of free-radical scavengers on activation of tubular cells. The TC-EC-S enhanced (p < 0.0001) migration of monocytes compared with TC-S. Both anti-TGF-beta and anti-MCP-1 antibodies partly inhibited (p < 0.0001) TC-EC-S-induced monocyte migration. The modified TC-EC-S (produced in the presence of superoxide dismutase [SOD], dimethyl thiourea [DMTU], or catalase, all scavengers of free radicals) induced lesser monocyte migration than did TC-EC-S alone. These results suggest that E. coli activates tubular cells to generate cytokines such as MCP-1 and TGF-beta that promote migration of monocytes. Free radicals such as superoxide and hydrogen peroxide may be acting as second messengers in E. coli-induced tubular cell activation.

Morphine-induced macrophage apoptosis modulates migration of macrophages: use of in vitro model of urinary tract infection.

Morphine has been reported to alter immune function. Morphine-induced macrophage apoptosis has been shown to contribute to altered immune status in an opiate milieu. We studied the effect of morphine-induced macrophage apoptosis on the migration of macrophages. Because urinary tract infection (UTI) is one of the commonest infections to evoke an inflammatory response; i.e., migration of neutrophils and monocytes to the site of infection, we used an in vitro model of UTI to test our hypothesis. We carried out both in vivo and in vitro studies. Mice of the FVB/N strain were treated with morphine for short (three doses, 24 hours) and long (11 doses, 96 hours) durations, and their bone marrow cells were isolated. In addition, apoptotic macrophages were prepared by heat treatment. To simulate the in vitro model of UTI, E. coli-activated tubular cell (TC)-conditioned medium containing transforming growth factor-beta (TGF-beta) and macrophage-monocyte chemoattractant protein-1 (MCP-1) was used to test migration of macrophages across a filter in a modified Boyden chamber. In addition, migration of macrophages into the peritoneal cavity was evaluated in both control and morphine-treated states. The effect of morphine on apoptosis as well as migration was studied in murine macrophages and bone marrow cells. Morphine not only promoted apoptosis of bone marrow cells (20% apoptotic cells) but also inhibited their migration across the filter. Control cells showed minimal apoptosis but displayed greater migration. Similarly, heat-treated (apoptotic) cells showed minimal migration. In peritoneal macrophage studies, morphine treatment retarded migration. Morphine inhibits macrophage migration both in vivo and in vitro. This attenuated transmigration of macrophages seems to be secondary to the apoptotic effect of morphine.

Neuroprotective activity of chemokines against N-methyl- d-aspartate or β-amyloid-induced toxicity in culture

We have examined the effect of various chemokines on neuronal toxicity in culture. In mixed cortical cultures, challenged with a brief pulse of N-methyl- d-aspartate (NMDA, 60 μM, 10 min), chemokines were either present for 2 h preceding the pulse or they were co-applied with NMDA and then kept in the medium for the following 20–24 h. Interleukin-8 (IL-8), regulated on activation of normal T cells expressed and secreted (RANTES) and macrophage/monocyte chemoattractant protein-1 (MCP-1), were neuroprotective under both conditions, whereas stromal cell-derived factor 1α (SDF-1α) was protective only when applied during and after the NMDA pulse. Mixed or pure neuronal cultures were also exposed for 48 h to a toxic fragment of the β-amyloid peptide (β-amyloid peptide-(25-35), 12.5 or 25 μM) in the absence or presence of chemokines. Among a number of chemokines, only RANTES was neuroprotective against β-amyloid peptide-(25-35)-induced neurotoxicity in both cultures. We conclude that activation of chemokine receptors differentially affects neuronal degeneration induced by excitotoxins or β-amyloid peptide in cortical cultures.

Tissue Factor Is Induced by Monocyte Chemoattractant Protein-1 in Human Aortic Smooth Muscle and THP-1 Cells

Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine thought to play a major role in recruiting monocytes to the atherosclerotic plaque. Tissue factor (TF), the initiator of coagulation, is found in the atherosclerotic plaque, macrophages, and human aortic smooth muscle cells (SMC). The exposure of TF during plaque rupture likely induces acute thrombosis, leading to myocardial infarction and stroke. This report demonstrates that MCP-1 induces the accumulation of TF mRNA and protein in SMC and in THP-1 myelomonocytic leukemia cells. MCP-1 also induces TF activity on the surface of human SMC. The induction of TF by MCP-1 in SMC is inhibited by pertussis toxin, suggesting that the SMC MCP-1 receptor is coupled to a Gi-protein. Chelation of intracellular calcium and inhibition of protein kinase C block the induction of TF by MCP-1, suggesting that in SMC it is mediated by activation of phospholipase C. SMC bind MCP-1 with a Kd similar to that previously reported for macrophages. However, mRNA encoding the macrophage MCP-1 receptors, CCR2A and B, is not present in SMC, indicating that they possess a distinct MCP-1 receptor. These data suggest that in addition to being a chemoattractant, MCP-1 may have a procoagulant function and raise the possibility of an autocrine pathway in which MCP-1, secreted by SMC and macrophages, induces TF activity in these same cells.

Enhanced expression and production of monocyte chemoattractant protein-1 in inflammatory bowel disease mucosa.

Peripheral blood monocytes are recruited to the inflamed mucosa of inflammatory bowel disease but the specific chemotactic signals responsible for their attraction are not known. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine with potent monocyte attracting and activating properties and the aim of this study was to examine its expression and production in inflammatory bowel disease. In situ hybridization demonstrated mRNA for MCP-1 in macrophages, some of which had been recently recruited from the circulation as demonstrated by their co-expression of the monocyte marker CD 14, as well as in smooth muscle and endothelial cells in inflamed mucosa. Immunohistochemical studies showed a corresponding distribution of MCP-1 protein production by macrophages, smooth muscle, and endothelial cells. By contrast minimal MCP-1 mRNA expression and protein were found in histologically normal mucosa. Macrophages isolated from surgically resected inflammatory bowel disease colons and examined by Northern analysis expressed MCP-1 mRNA significantly more frequently (15/24 vs. 0/19, P< 0.0001) than macrophages from histologically normal mucosa from colon cancer resections. Blood monocytes stimulated by lipopolysaccharide and treated with hydrocortisone, 5-aminosalicylic acid, or cyclosporin A showed reduced MCP-1 expression and production in the presence of these agents. This study demonstrates increased expression of MCP-1 mRNA and protein and cells of origin of MCP-1 in inflamed intestinal mucosa. Together with the demonstrated influence of therapeutic agents on monocyte MCP-1 production the findings suggest a role for MCP-1 in monocyte attraction to the mucosal lesion of inflammatory bowel disease.