Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80098 (monocyte chemoattractant protein)
 1,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokines such as monocyte chemoattractant protein (MCP) -1 and interleukin (IL)-8 are known to be involved in various processes in atherosclerosis such as plaque formation, plaque rupture, and thrombus formation. We investigated whether a new chemokine, Leukotactin (LKN)-1, is involved in atherosclerosis. We tested the expression of LKN-1 by immunohistochemical methods in carotid atherosclerotic plaque specimen. Induction of pro-inflammatory cytokines, transmigration, and tissue factor (TF) expression were tested in THP-1 cells and human peripheral blood monocytes treated with recombinant human LKN-1. Immunohistochemical analyses revealed that expression of LKN-1 occurs in regions of plaques rich in foam cells. In a Boyden chamber assay, THP-1 cells treated with 0.01--10 nM of LKN-1 transmigrated through gelatin coated filters in a dose dependent manner. LKN-1 also induced the transient expression of TNF-alpha, IL-8, and MCP-1 within 15 min of the treatment of the THP-1 cells. When peripheral blood monocytes were treated with LKN-1, expression levels of TF and TF-mediated procoagulating activity were induced in a time- and dose-dependent manner. These results raise the possibility that LKN-1 is another chemokine that is involved in the atherogenesis. LKN-1 may chemoattract immune cells into the plaque, induce pro-inflammatory cytokines, and produce thrombi by inducing TF expression.
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PMID:A novel chemokine, Leukotactin-1, induces chemotaxis, pro-atherogenic cytokines, and tissue factor expression in atherosclerosis. 1188 7

Macrophages play an important role in the pathogenesis of atherosclerosis, for which monocyte chemoattractant protein (MCP)-1 and CCR2 chemokine receptors may be involved. The authors have recently demonstrated that propagermanium exerts inhibitory effect on the CCR2 receptors. In the current study, the authors examined whether the organic germanium suppresses the MCP-1-induced monocyte migration in vitro and the development of atherosclerosis in WHHL rabbits in vivo. In the in vitro experiment, propagermanium concentration-dependently suppressed the MCP-1-induced migration of THP-1 cells. In the in vivo experiment, 20 WHHL rabbits were randomly divided into two groups; one group was treated with oral administration with propagermanium (9 mg/kg/day) for 3 months, and another group served as a control (n = 10 each). After 3 months, the aorta was isolated and stained with oil red O staining, and neointimal formation was quantified. Macrophage accumulation in the aorta was also evaluated by immunostaining. Long-term treatment with propagermanium did not affect the serum lipid profiles. However, the treatment significantly suppressed the oil red O-positive area of the total aorta (p < 0.05). Similarly, propagermanium significantly suppressed the intimal lesions (maximal intimal thickness and intimal area) and macrophage staining-positive area (all p < 0.05). A significant positive correlation was noted between macrophage staining-positive area and intimal lesions (p < 0.0001). These results indicate that long-term treatment with propagermanium suppresses the development of atherosclerosis in WHHL rabbits, suggesting its usefulness for the treatment of atherosclerotic vascular disease in humans.
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PMID:Long-term treatment with propagermanium suppresses atherosclerosis in WHHL rabbits. 1254 76

Pneumolysin is an important virulence factor of Streptococcus pneumoniae, interacting with the membranes of host cells to elicit a multitude of inflammatory responses. We used cDNA microarrays to identify genes which are responsive to S. pneumoniae in a pneumolysin-dependent and -independent fashion. The THP-1 human monocytic cell line was coincubated for 3 h with medium alone, with the virulent type 2 S. pneumoniae strain D39, or with the isogenic strain PLN, which does not express pneumolysin. RNA was isolated from the monocytes and hybridized on cDNA microarrays. Of 4,133 genes evaluated, 142 were found to be responsive in a pneumolysin-dependent fashion, whereas 40 were found to be responsive independent of pneumolysin. Genes that were up-regulated in cells exposed to D39 relative to those exposed to PLN included genes encoding proteins such as mannose binding lectin 1, lysozyme, alpha-1 catenin, cadherin 17, caspases 4 and 6, macrophage inflammatory protein 1beta (MIP-1beta), interleukin 8 (IL-8), monocyte chemotactic protein 3 (MCP-3), IL-2 receptor beta (IL-2Rbeta), IL-15 receptor alpha (IL-15Ralpha), interferon receptor 2, and prostaglandin E synthase. Down-regulated genes included those encoding complement component receptor 2/CD21, platelet-activating factor acetylhydrolase, and oxidized low-density lipoprotein receptor 1 (OLR1). Pneumolysin-independent responses included down-regulation of the genes encoding CD68, CD53, CD24, transforming growth factor beta2, and signal transducers and activators of transcription 1. These results demonstrate the striking effects of pneumolysin on the host cell upon exposure to S. pneumoniae.
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PMID:Pneumolysin-dependent and -independent gene expression identified by cDNA microarray analysis of THP-1 human mononuclear cells stimulated by Streptococcus pneumoniae. 1265 30

Endotoxins displaying differences in the chemical structure of their lipid A were used to induce the expression of chemokines in the human monocytic THP-1 cell line. LPS from two enterobacterial species such as Escherichia coli and Yersinia enterocolitica induced mRNA expression of IFN-gamma-inducible protein (IP)-10, macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, monocyte chemoattractant protein (MCP)-1 and IL-8. LPS from the non-enterobacterial genera Brucella and Ochrobactrum induced the expression of these chemokines to a lower extent. Attempts to address the signaling routes involved in these responses were carried out in transiently transfected HEK293 cells. Induction of kappaB-driven transcriptional activity by enterobacterial LPS was observed in cells transfected with TLR-4 alone, although co-transfection of TLR-4, MD-2 and CD14 provided optimal induction. The response to Brucella spp. and Ochrobactrum anthropi LPS was only significant at the concentration of 10 microg/ml. These data indicate that LPS from Brucella spp. and O. anthropi, which contain lipid A moieties with structural features different from those of Enterobacteriaceae elicit biochemical signaling via TLR-4 only at high concentrations. Neither TLR-1, TLR-2 and TLR-6 nor heterodimeric combinations of these receptor molecules are involved. Conversely, the ability of LPS to activate the TLR-4 route is a reliable molecular biomarker for endotoxicity.
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PMID:Interaction of endotoxins with Toll-like receptor 4 correlates with their endotoxic potential and may explain the proinflammatory effect of Brucella spp. LPS. 1533 79

Benidipine hydrochloride (benidipine) is a dihydropyridine-Ca2+ channel blocker with antioxidant properties. We examined the effects of benidipine on cytokine-induced expression of adhesion molecules and chemokines, which play important roles in the adhesion of monocytes to endothelium. Pretreatment of human aortic endothelial cells (HAECs) with benidipine (0.3-10 micromol/l) for 24 h significantly suppressed cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) mRNA and protein expression, resulting in reduced adhesion of THP-1 monocytes. Benidipine also suppressed induction of monocyte chemoattractant protein (MCP)-1 and interleukin-8. Benidipine inhibited redox-sensitive transcriptional nuclear factor-kappaB (NF-kappaB) pathway, as determined by Western blotting of inhibitory kappaB (IkappaB) phosphorylation and luciferase reporter assay. Results of analysis using optical isomers of benidipine and antioxidants suggested that these inhibitory effects were dependent on pharmacological effects other than Ca2+ antagonism such as antioxidant effects. Benidipine may thus have anti-inflammatory properties and benefits for in the treatment of atherosclerosis.
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PMID:Effects of benidipine, a dihydropyridine-Ca2+ channel blocker, on expression of cytokine-induced adhesion molecules and chemoattractants in human aortic endothelial cells. 1536 9

TL1A (VEGI/TNFSF15) is the ligand for DR3 (TNFRSF12) and is a newly identified member of the tumor necrosis factor superfamily (TNFSF). Previously, DR3 has been shown to have a role in atherogenesis through stimulation of matrix degrading enzymes including matrix metalloproteinase (MMP)-9. Immunohistochemical staining of human carotid atherosclerotic plaques revealed a high-level expression of TL1A in regions rich in macrophage/foam cells. To investigate the role of TL1A and DR3 in the functioning of macrophage/foam cells in relation to atherogenesis, we have analyzed cellular events mediated by TL1A and DR3 in a human macrophage-like cell line, THP-1. Treatment of THP-1 cells with immobilized anti-DR3 monoclonal antibody in combination with IFN-gamma caused induction of pro-atherogenic cytokines/chemokines such as TNF-alpha, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8. Treatment of THP-1 cells with recombinant TL1A in combination with IFN-gamma also caused induction of MMP-9 and IL-8. Furthermore, the expression of DR3 in peripheral blood monocytes was induced after atherogenic stimulation. These data suggest that TL1A and DR3 is involved in atherosclerosis via the induction of pro-inflammatory cytokines/chemokines and decreasing plaque stability by inducing extracellular matrix degrading enzymes.
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PMID:Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis. 1576 Jun 79

The biological response to endotoxin mediated through the Toll-like receptor 4 (TLR4)-MD-2 receptor complex is directly related to lipid A structure or configuration. Endotoxin structure may also influence activation of the MyD88-dependent and -independent signaling pathways of TLR4. To address this possibility, human macrophage-like cell lines (THP-1, U937, and MM6) or murine macrophage RAW 264.7 cells were stimulated with picomolar concentrations of highly purified endotoxins. Harvested supernatants from previously stimulated cells were also used to stimulate RAW 264.7 or 23ScCr (TLR4-deficient) macrophages (i.e., indirect induction). Neisseria meningitidis lipooligosaccharide (LOS) was a potent direct inducer of the MyD88-dependent pathway molecules tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 3alpha (MIP-3alpha), and the MyD88-independent molecules beta interferon (IFN-beta), nitric oxide, and IFN-gamma-inducible protein 10 (IP-10). Escherichia coli 55:B5 and Vibrio cholerae lipopolysaccharides (LPSs) at the same pmole/ml lipid A concentrations induced comparable levels of TNF-alpha, IL-1beta, and MIP-3alpha, but significantly less IFN-beta, nitric oxide, and IP-10. In contrast, LPS from Salmonella enterica serovars Minnesota and Typhimurium induced amounts of IFN-beta, nitric oxide, and IP-10 similar to meningococcal LOS but much less TNF-alpha and MIP-3alpha in time course and dose-response experiments. No MyD88-dependent or -independent response to endotoxin was seen in TLR4-deficient cell lines (C3H/HeJ and 23ScCr) and response was restored in TLR4-MD-2-transfected human embryonic kidney 293 cells. Blocking the MyD88-dependent pathway by DNMyD88 resulted in significant reduction of TNF-alpha release but did not influence nitric oxide release. IFN-beta polyclonal antibody and IFN-alpha/beta receptor 1 antibody significantly reduced nitric oxide release. N. meningitidis endotoxin was a potent agonist of both the MyD88-dependent and -independent signaling pathways of the TLR4 receptor complex of human macrophages. E. coli 55:B5 and Vibrio cholerae LPS, at the same picomolar lipid A concentrations, selectively induced the MyD88-dependent pathway, while Salmonella LPS activated the MyD88-independent pathway.
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PMID:Differential induction of the toll-like receptor 4-MyD88-dependent and -independent signaling pathways by endotoxins. 1584

Novel analogs of human monocyte chemoattractant protein 1 (MCP-1) were designed, synthesized and characterized to be used as tools to generate monoclonal antibodies as potential human therapeutics. MCP-1 and three analogs were synthesized by step-wise Fmoc solid phase synthesis. After oxidation to form the two-disulfide bonds, affinity chromatography using an immobilized mouse anti-human MCP-1 monoclonal antibody (mAb) was utilized for a simple and highly effective purification procedure for the proteins. The final products were extensively characterized and compared with recombinant human MCP-1 (rhMCP-1). All proteins showed identical binding with mouse anti-human MCP-1 mAbs as measured by surface plasmon resonance. Synthetic MCP-1 and the analogs were comparable to recombinant MCP-1 in competition radio-ligand binding to CCR2 receptors on THP-1 cells, and MCP-1-induced, calcium mobilization and chemotaxis assays.
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PMID:Synthesis and biological characterization of human monocyte chemoattractant protein 1 (MCP-1) and its analogs. 1594 31

The clinical picture of severe acute respiratory syndrome (SARS) is characterized by pulmonary inflammation and respiratory failure, resembling that of acute respiratory distress syndrome. However, the events that lead to the recruitment of leukocytes are poorly understood. To study the cellular response in the acute phase of SARS coronavirus (SARS-CoV)-host cell interaction, we investigated the induction of chemokines, adhesion molecules, and DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin) by SARS-CoV. Immunohistochemistry revealed neutrophil, macrophage, and CD8 T-cell infiltration in the lung autopsy of a SARS patient who died during the acute phase of illness. Additionally, pneumocytes and macrophages in the patient's lung expressed P-selectin and DC-SIGN. In in vitro study, we showed that the A549 and THP-1 cell lines were susceptible to SARS-CoV. A549 cells produced CCL2/monocyte chemoattractant protein 1 (MCP-1) and CXCL8/interleukin-8 (IL-8) after interaction with SARS-CoV and expressed P-selectin and VCAM-1. Moreover, SARS-CoV induced THP-1 cells to express CCL2/MCP-1, CXCL8/IL-8, CCL3/MIP-1alpha, CXCL10/IP-10, CCL4/MIP-1beta, and CCL5/RANTES, which attracted neutrophils, monocytes, and activated T cells in a chemotaxis assay. We also demonstrated that DC-SIGN was inducible in THP-1 as well as A549 cells after SARS-CoV infection. Our in vitro experiments modeling infection in humans together with the study of a lung biopsy of a patient who died during the early phase of infection demonstrated that SARS-CoV, through a dynamic interaction with lung epithelial cells and monocytic cells, creates an environment conducive for immune cell migration and accumulation that eventually leads to lung injury.
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PMID:Modeling the early events of severe acute respiratory syndrome coronavirus infection in vitro. 1650 Oct 78

Chronic renal failure (CRF) patients display an immunodeficiency state, and uremic solutes that accumulate during CRF may be involved in this immunodeficiency. In this study, we examined whether the uremic solute para-cresol (p-cresol), at concentrations similar to those found in patients, alters leukocyte transmigration in vitro. We found that p-cresol significantly inhibited monocyte THP-1 cell line and PBMCs transmigration across IL-1beta-stimulated human umbilical vein endothelial cell (HUVEC) in a static two-compartment model. This inhibitory effect of p-cresol persisted in the presence of a physiologic concentration of human serum albumin. In order to investigate the mechanism involved, expression of endothelial chemokines, fractalkine, monocyte chemoattractant protein 1 (MCP-1) and IL-8 and membrane expression of junctional adhesion molecule A (JAM-A or JAM-1) were studied. We found that p-cresol decreased mRNA expression of the chemokine fractalkine in IL-1beta-stimulated HUVEC, without modifying mRNA expression of MCP-1 and IL-8. In addition, p-cresol decreased IL-1beta-induced expression of membrane-bound and soluble forms of fractalkine and impaired the membrane expression of JAM-A. Taken together, these results suggest that p-cresol, by impairing leukocyte transendothelial migration, plays a role in the immune dysfunction of uremic patients.
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PMID:The uremic solute p-cresol decreases leukocyte transendothelial migration in vitro. 1695 66


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