UNIPROT:P80098 - FACTA Search

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Query: UNIPROT:P80098 (monocyte chemoattractant protein)
1,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recruitment of monocytes into the arterial wall is one of the earliest events in the pathogenesis of atherosclerosis. Since monocyte chemoattractant protein 1 (MCP-1) plays a key role in the subendothelial recruitment of monocytes, we tested whether nitric oxide (NO) modulates the expression of MCP-1 in cultured human endothelial cells. Inhibition of basal NO production by NG-nitro-L-arginine (L-NAG) upregulates endothelial MCP-1 mRNA expression (250 +/- 20%) and protein secretion. Exogenous addition of NO dose-dependently decreased MCP-1 mRNA expression and secretion. Changes in MCP-1 mRNA expression and protein secretion were paralleled by corresponding changes in chemotactic activity of cell-conditioned media for monocytes. An MCP-1 antibody reduced monocyte chemotactic activity by 85% and completely abolished the increased monocyte chemotactic activity induced by the inhibition of NO production. Elevation of endothelial cGMP levels had no significant effect on MCP-1 mRNA expression. Inhibition of basal endothelial NO production by L-NAG increased binding activity of a nuclear factor kappa B (NF-kappa B)-like transcriptional regulatory factor, whereas exogenous addition of NO decreased NF-kappa B-like binding activity during stimulation with tumor necrosis factor-alpha. Thus, NO modulates MCP-1 expression and monocyte chemotactic activity secreted by human umbilical vein endothelial cells (HUVECs) in culture. The activation of NF-kappa B-like transcriptional regulatory proteins by inhibition of NO suggests a molecular link between an oxidant-sensitive transcriptional regulatory mechanism and NO synthesis in HUVECs.
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PMID:Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. 775 69

The early atherosclerotic lesion is characterized by the migration of inflammatory cells, including monocytes, which may serve as a source of cytokines such as monocyte chemoattractant protein 1 (MCP-1), a homologue of mouse JE. We investigated the effect of MCP-1 on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. In Northern blot analysis, MCP-1/JE transcripts were not observed in unstimulated VSMC, but its expression was clearly observed by exposure to lipopolysaccharide (1 micrograms/ml) for 6 h. Human recombinant MCP-1 inhibited the uptake of [3H]thymidine by VSMC cultured in 0.5% fetal bovine serum (FBS) containing Dulbecco's modified Eagle's medium (DMEM) in a dose-dependent manner. The inhibitory effect of MCP-1 on the growth of VSMC was also confirmed by a change in cell counts. The antiproliferative effect of MCP-1 was significantly blocked in the presence of an anti-MCP-1 antibody. MCP-1-induced inhibition of [3H]thymidine uptake was not affected in the presence of indomethacin (1 micrograms/ml) or NG-monomethyl-L-arginine (0.1 mM), and MCP-1 showed no effect on 6-ketoprostaglandin F1 alpha, guanosine 3',5'-cyclic monophosphate, and adenosine 3',5'-cyclic monophosphate syntheses in VSMC. These results indicate that MCP-1 inhibits the proliferation of VSMC in vitro and that its effect is independent of prostaglandin or nitric oxide generation.
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PMID:Monocyte chemoattractant protein 1 inhibits growth of rat vascular smooth muscle cells. 790 Aug 56

Traumatic injury to the brain initiates multiple interrelated processes that involve parenchymal, vascular, and infiltrating inflammatory cells. Nitric oxide (NO) and chemokines have been implicated as regulators of the central nervous system injury response. Following a cryogenic lesion of the cerebral cortex in mice, mRNA for NO synthase (NOS)-2 was detected by reverse transcriptase polymerase chain reaction ipsilaterally 12 h after injury and persisted for 2 weeks. While mRNA was also detected contralaterally, the time course of expression was shorter (1 week). By immunohistochemistry, NOS-2 protein was initially detected ipsilaterally 12 h after injury in infiltrating inflammatory cells. Astroglial cells expressed NOS-2 from 24 to 72 h after injury. The expression of monocyte chemoattractant protein (MCP-1) mRNA peaked at 6 h on the lesion side, remained for 24 h and then declined by 48 h. On the unlesioned side, MCP-1 mRNA was expressed to a much lesser extent and had declined by 24 h. The up-regulation of MCP-1 was relatively specific as a closely related mRNA encoding IP-10 was not significantly increased. These findings implicate a role for NOS-2 and MCP-1 as potential regulators of cellular events following cryogenic cerebral trauma.
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PMID:Expression of monocyte chemoattractant protein (MCP-1) and nitric oxide synthase-2 following cerebral trauma. 945 27

This study demonstrates that the therapeutic effect of a nitric oxide inhibitor in a murine model of fecal peritonitis is mediated in part by increased levels of interleukin-10 (IL-10) and monocyte chemoattractant protein 1 (MCP-1). Female CD1 mice were subjected to cecal ligation and puncture (CLP) with a 21-gauge needle and, immediately following surgery, were injected intraperitoneally with saline, N(G)-nitro-L-arginine methyl ester (L-NAME; 8 mg/kg), or N(G)-nitro-D-arginine methyl ester (D-NAME; 8 mg/kg). At 96 h after surgery and drug treatment, 20% of mice that received D-NAME had survived whereas 60% of mice that received L-NAME were alive. To elucidate the effect of L-NAME treatment on chemokine and cytokine production during fecal peritonitis, the levels of macrophage inflammatory protein 2 (MIP-2), IL-10, and MCP-1 were measured in peritoneal washings from additional groups of mice 24 h after the CLP surgery. Peritoneal fluids from L-NAME-treated mice contained significantly higher levels of IL-10 and MCP-1 than did those from D-NAME-treated mice. To elucidate the effect of nitric oxide inhibition on potential cellular sources of IL-10 and MCP-1 in the CLP model, cultured alveolar and peritoneal macrophages were activated with bacterial lipopolysaccharide in the presence of L-NAME; these macrophages produced significantly more MCP-1 than did similarly activated macrophages in the presence of D-NAME. In the CLP surgery model, immunoneutralization of IL-10 alone or IL-10 and MCP-1 together with polyclonal antibodies prior to surgery significantly reduced the survival rates in L-NAME-treated groups compared with L-NAME-treated groups that received preimmune serum. Taken together, these data demonstrate that the inhibition of nitric oxide following experimental CLP fecal peritonitis is therapeutic, in part through the modulatory effect of this treatment on the synthesis of IL-10 and MCP-1.
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PMID:Therapeutic effects of nitric oxide inhibition during experimental fecal peritonitis: role of interleukin-10 and monocyte chemoattractant protein 1. 945 22

An intact chemotactic response is vital for leukocyte trafficking and host defense. Opiates are known to exert a number of immunomodulating effects in vitro and in vivo, and we sought to determine whether they were capable of inhibiting chemokine-induced directional migration of human leukocytes, and if so, to ascertain the mechanism involved. The endogenous opioid met-enkephalin induced monocyte chemotaxis in a pertussis toxin-sensitive manner. Met-enkephalin, as well as morphine, inhibited IL-8-induced chemotaxis of human neutrophils and macrophage inflammatory protein (MIP)-1alpha, regulated upon activation, normal T expressed and secreted (RANTES), and monocyte chemoattractant protein 1, but not MIP-1beta-induced chemotaxis of human monocytes. This inhibition of chemotaxis was mediated by delta and micro but not kappa G protein-coupled opiate receptors. Calcium flux induced by chemokines was unaffected by met-enkephalin pretreatment. Unlike other opiate-induced changes in leukocyte function, the inhibition of chemotaxis was not mediated by nitric oxide. Opiates induced phosphorylation of the chemokine receptors CXCR1 and CXCR2, but neither induced internalization of chemokine receptors nor perturbed chemokine binding. Thus, inhibition of chemokine-induced chemotaxis by opiates is due to heterologous desensitization through phosphorylation of chemokine receptors. This may contribute to the defects in host defense seen with opiate abuse and has important implications for immunomodulation induced by several endogenous neuropeptides which act through G protein-coupled receptors.
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PMID:Opiates transdeactivate chemokine receptors: delta and mu opiate receptor-mediated heterologous desensitization. 967 44

Recent studies support the concept that pulmonary granulomatous inflammation directed by interferon (IFN)-gamma, interleukin (IL)-12, and nitric oxide usually resolves in the absence of fibrosis. To determine whether nitric oxide participates in modulating the fibrotic response during the development of pulmonary granulomas in response to purified protein derivative (PPD), mice presensitized to PPD received daily intraperitoneal injections of N(G)-nitro-D-arginine-methyl ester (D-NAME), N(G)-nitro-L-arginine-methyl ester (L-NAME), or aminoguanidine after delivery of PPD-coated beads to the lungs. Eight days later, morphometric analysis of lung granulomas revealed that L-NAME-treated mice when challenged with PPD in vitro for 36 hours had the largest pulmonary granulomas and the greatest collagen deposition among the treated groups. In addition, equivalent numbers of dispersed lung cells from L-NAME- and aminoguanidine-treated mice produced significantly higher levels of IL-4, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1alpha and significantly lower levels of eotaxin compared with D-NAME-treated mice. Cultures of dispersed lung cells from L-NAME-treated mice also produced significantly more IL-10 and less IL-12 compared with similar numbers of dispersed lung cells from D-NAME-treated mice. Cultures of isolated lung fibroblasts from L-NAME-treated mice expressed higher levels of C-C chemokine receptor 2 (CCR2) and CCR3 mRNA and contained less MCP-1 and eotaxin protein than a similar number of fibroblasts from D-NAME-treated mice. Thus, nitric oxide appears to regulate the deposition of extracellular matrix in lung granulomas through the modulation of the cytokine and chemokine profile of these lesions. Alterations in the cytokine, chemokine, and procollagen profile of this lesion may be a direct effect of nitric oxide on the pulmonary fibroblast and provide an important signal for regulating fibroblast activity during the evolution of chronic lung disease.
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PMID:Collagen deposition in a non-fibrotic lung granuloma model after nitric oxide inhibition. 984 76

Nitric oxide (NO) produced by cytokine-activated macrophages is reported to be cytotoxic against the helminth Schistosoma mansoni, although this is a controversial issue. Previous work in our laboratory identified a fraction of S. mansoni soluble adult worm antigenic preparation (SWAP), named PIII, able to elicit significant in vitro cell proliferation and at the same time lower in vitro and in vivo granuloma formation when compared either to soluble egg antigen (SEA) or to SWAP. Here we report that, in comparison to other S. mansoni antigenic preparations (SEA and SWAP), supernatants of PBMC cultivated with PIII possess higher concentrations of interleukin-10 (IL-10) and macrophage inflammatory protein (MIP-1alpha), concomitantly with lower concentrations of monocyte chemoattractant protein (MCP-1) and regulated on activation, normal T expressed and secreted (RANTES). In the particular case of NO inhibition, supernatants of PBMC cultivated with PIII present decreased IL-10 levels. Altogether, these results indicate that IL-10, MIP-1alpha, MCP-1 and RANTES are distinctively important elements in the PIII modulating role, while NO seems to be pivotal in the regulation of granulomatous responses.
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PMID:Nitric oxide interaction with IL-10, MIP-1alpha, MCP-1 and RANTES over the in vitro granuloma formation against different Schistosoma mansoni antigenic preparations on human schistosomiasis. 1081 Dec 80

The aim of this study was to estimate the contributions of dietary n-3 polyunsaturated fatty acid (PUFA), a representative dietary immunosuppressant, to the activity of both alveolar macrophages (AM) and natural killer (NK) cells, and compare them to those of n-6 PUFA. Twelve 5-week-old female Sprague-Dawley rats were divided into two dietary groups, one fed a 10% fat diet for 9 weeks enriched with n-3 PUFA (n-3 diet) and the other an n-6 PUFA (n-6 diet). AM reduced the release of nitric oxide, monocyte chemoattractant protein 1 and tumor necrosis factor alpha in the rats fed the n-3 diet, compared with rats fed the n-6 diet. NK cell activity was reduced by consumption of the n-3 diet. This study suggests that consumption of n-3 PUFA can ameliorate pulmonary inflammatory disorders which are affected by the reduction of not only proinflammatory cytokines but also chemokine released from AM.
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PMID:Dietary n-3 polyunsaturated fatty acid and status of immunocompetent cells involved in innate immunity in female rats. 1083 65

The coexistence of hypercholesterolaemia and diabetes dramatically and synergistically increases the risk of microvascular and macrovascular complications in patients. A single unifying mechanism of increased production of reactive oxygen species (ROS) by angiotensin II (Ang II) may serve as a causal link between hyperglycaemia and hypercholesterolaemia and many of the major pathways responsible for atherogenic and diabetic disorders. Several lines of evidence suggest a crucial role for Ang II-mediated oxidative stress in the pathogenesis of hyperglycaemia- and hypercholesterolemia-associated endothelial dysfunction. Endothelial dysfunction in these scenarios may be due to impaired nitric oxide (NO) synthesis and/or inactivation of endothelium-derived NO by ROS. That Ang II plays an important role in the development of atherosclerosis and glomerulosclerosis is supported by numerous studies indicating that angiotensin receptor blockers (ARBs) retard the progression of these diseases in both experimental animal models and humans. Evidence indicates that Ang II contributes to atherogenesis at both transcriptional and translational levels by upregulating adhesion molecule mRNA and protein synthesis. The recent demonstration of Ang II AT(2) receptors in the adult kidney and their potential to oppose the vasoconstrictive, antinatriuretic, and profibrotic properties of AT(1) receptors suggests that the balance of intrarenal AT(1) and AT(2) receptors may be important in determining the cellular responses to Ang II in diabetic nephropathy. Results of these studies suggest that hypercholesterolaemia and hyperglycaemia can induce a pro-inflammatory response within coronary arteries and the kidney glomerulus. This response involves production of well described macrophage chemotactic and adhesion molecules, which results in macrophage recruitment and the development of acute and chronic injury. Glomerular macrophage recruitment in experimental diabetes occurs via Ang II-stimulated monocyte chemoattractant protein (MCP)-1 expression, suggesting that the renin-angiotensin system is an important regulator of local MCP-1 expression, and strongly implicating macrophage recruitment and activation in the pathogenesis of early diabetic glomerular injury. Diabetes-associated vascular complications may also involve an activation of the nuclear factor (NF)-kappaB by hyperglycaemia. NF-kappaB activation is related to AT(1) receptor-mediated pathways, and is believed to be dependent on activation of the Rho proteins belonging to the superfamily of low molecular weight guanosine triphosphatases (GTPases) that regulate intracellular signalling. Preincubation of vascular smooth muscle cells with insulin doubled NF-kappaB transactivation stimulated by Ang II and hyperglycaemia, suggesting a potential mechanism for crosstalk between the renin-angiotensin system and hyperglycaemia. Taken together, these data suggest that activation of the renin-angiotensin system is a mechanism for the initiation and progression of inflammatory cell infiltration found in early changes common to both hypercholesterolaemia and hyperglycaemia. While the base of information regarding ARBs in high-risk patients with diabetes and hypercholesterolemia is lacking, preclinical and pilot trial data suggest that the ARBs are reno- and vasculoprotective in these patients. Therapeutic blockade of Ang II AT(1) receptors in diabetic and hypercholesterolaemic humans by ARBs, with concomitant elevation in plasma and tissue Ang II levels, may provide vascular and renal protection not only by reducing AT(1) receptor-mediated pro-oxidative effects, but also by unopposed AT(2) receptor stimulation.
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PMID:[Pathophysiological and clinical implications of AT(1) and AT(2) angiotensin II receptors in metabolic disorders: hypercholesterolaemia and diabetes]. 1203 87

An estimated one-third of the world's population is latently infected with Mycobacterium tuberculosis, the etiologic agent of tuberculosis. Here, we demonstrate that, unlike wild-type M. tuberculosis, a strain of M. tuberculosis disrupted in the mce1 operon was unable to enter a stable persistent state of infection in mouse lungs. Instead, the mutant continued to replicate and killed the mice more rapidly than did the wild-type strain. Histological examination of mouse lungs infected with the mutant strain revealed diffusely organized granulomas with aberrant inflammatory cell migration. Murine macrophages infected ex vivo with the mutant strain were reduced in their ability to produce tumor necrosis factor alpha, IL-6, monocyte chemoattractant protein 1, and nitric oxide (NO), but not IL-4. The mce1 mutant strain complemented with the mce1 genes stimulated tumor necrosis factor alpha and NO production by murine macrophages at levels stimulated by the wild-type strain. These observations indicate that the mce1 operon mutant is unable to stimulate T helper 1-type immunity in mice. The hypervirulence of the mutant strain may have resulted from its inability to stimulate a proinflammatory response that would otherwise induce organized granuloma formation and control the infection without killing the organism. The mce1 operon of M. tuberculosis may be involved in modulating the host inflammatory response in such a way that the bacterium can enter a persistent state without being eliminated or causing disease in the host.
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PMID:Hypervirulent mutant of Mycobacterium tuberculosis resulting from disruption of the mce1 operon. 1466 45

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