Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Sixteen healthy subjects were intravenously injected with lipopolysaccharide (LPS), once with placebo and once with recombinant human interleukin (IL)-10 (25 microgram/kg), to determine the effect of IL-10 on LPS-induced production of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1. LPS induced transient increases in serum MIP-1alpha, MIP-1beta, and MCP-1. Pretreatment with IL-10 inhibited LPS-induced release of MIP-1alpha, MIP-1beta, and MCP-1. In whole blood in vitro, the IL-10-induced inhibition of MIP-1alpha and MIP-1beta release was equally potent in the presence or absence of an anti-tumor necrosis factor (TNF) antibody. Although isolated peripheral blood mononuclear cells produced more MIP-1alpha and MIP-1beta than neutrophils, the latter cells were more sensitive to the inhibiting effect of IL-10. IL-10 attenuates LPS-induced production of CC chemokines in human endotoxemia, whereby in vitro experiments suggest that, in the case of MIP-1alpha and MIP-1beta release, this effect is independent from an inhibitory effect on TNF production.
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PMID:Interleukin 10 inhibits the release of CC chemokines during human endotoxemia. 1066 45

Thalidomide, a psychoactive drug that readily crosses the blood-brain barrier, has been shown to possess immunomodulatory attributes, including the inhibition of cytokine production by monocytes and microglia. In this study, we investigated the effect of thalidomide on chemokine production by human microglial cells. Microglial cells were stimulated with lipopolysaccharide, a key cell-wall component of gram-negative bacteria responsible for meningitis, and production of chemokines (regulated upon activation normally T cell expressed and secreted [RANTES], monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1beta, and interleukin [IL]-8) was examined by ELISA. Thalidomide treatment was found to cause potent and selective inhibition of IL-8 production in a dose-responsive manner. This inhibition was associated with decreased intracellular IL-8 staining as well as reduced transcription of IL-8 mRNA. In addition, thalidomide treatment of lipopolysaccharide-stimulated microglia inhibited the activation of protein NF-kappaB, a transcription factor known to be important for IL-8 production. These results suggest thalidomide could have a therapeutic role in acute bacterial meningitis through inhibition of IL-8-mediated neutrophil chemotaxis.
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PMID:Effect of thalidomide on chemokine production by human microglia. 1095 Aug 3

We characterized the expression of the beta-chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES by primary human microglia after exposure to Cryptococcus neoformans. In the absence of specific antibody, C. neoformans failed to elicit a chemokine response, while in the presence of specific antibody, microglia produced MIP-1alpha and MIP-1beta in amounts comparable to those induced by lipopolysaccharide. RANTES was also induced but at much lower levels. In addition to MIP-1alpha and MIP-1beta mRNA, we observed a robust induction of monocyte chemoattractant protein 1 and interleukin-8 mRNA following incubation of microglia with opsonized C. neoformans. In contrast, cryptococcal polysaccharide did not induce a chemokine response even when specific antibody was present and inhibited the MIP-1alpha induction associated with antibody-mediated phagocytosis of C. neoformans. The role of the Fc receptor in the observed chemokine induction was explored in several experiments. Treatment of microglia with cytochalasin D inhibited internalization of C. neoformans but did not affect MIP-1alpha induction. In contrast, treatment with herbimycin A, a tyrosine kinase inhibitor, inhibited MIP-1alpha induction. Microglia stimulated with immobilized murine immunoglobulin also produced MIP-1alpha and RANTES (MIP-1alpha > RANTES). Our results show that microglia produce several chemokines when stimulated by C. neoformans in the presence of specific antibody and that this process is likely to be mediated by Fc receptor activation. This response can be down-regulated by cryptococcal capsular polysaccharide. These findings suggest a mechanism by which C. neoformans infections fail to induce strong inflammatory responses in patients with cryptococcal meningoencephalitis and have important implications for antibody therapy.
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PMID:Cryptococcus neoformans induces macrophage inflammatory protein 1alpha (MIP-1alpha) and MIP-1beta in human microglia: role of specific antibody and soluble capsular polysaccharide. 1117 58

Macrophages secrete matrix metalloproteinase 9 (MMP-9), an enzyme that weakens the fibrous cap of atherosclerotic plaques, predisposing them to plaque rupture and subsequent ischemic events. Recent work indicates that statins strongly reduce the possibility of heart attack. Furthermore, these compounds appear to exert beneficial effects not only by lowering plasma low-density-lipoprotein cholesterol but also by directly affecting the artery wall. To evaluate whether statins influence the proinflammatory responses of monocytic cells, we studied their effects on the chemotactic migration and MMP-9 secretion of human monocytic cell line THP-1. Simvastatin dose dependently inhibited THP-1 cell migration mediated by monocyte chemoattractant protein 1, with a 50% inhibitory concentration of about 50 nM. It also inhibited bacterial lipopolysaccharide-stimulated secretion of MMP-9. The effects of simvastatin were completely reversed by mevalonate and its derivatives, farnesylpyrophosphate and geranylgeranyl pyrophosphate, but not by ubiquinone. Additional studies revealed similar but more profound inhibitory effects with L-839,867, a specific inhibitor of geranylgeranyl transferase. However, alpha-hydroxyfarnesyl phosphonic acid, an inhibitor of farnesyl transferase, had no effect. C3 exoenzyme, a specific inhibitor of the prenylated small signaling Rho proteins, mimicked the inhibitory effects of simvastatin and L-839,867. These data supported the role of geranylgeranylation in the migration and MMP-9 secretion of monocytes.
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PMID:Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation. 1140 82

This study investigated the endotoxic and biological properties of purified lipopolysaccharide (LPS) isolated from an oral spirochete, Treponema pectinovorum. Endotoxicity, measured by Limulus amoebocyte lysate kinetic assay, showed that the LPS contained 1.28 endotoxin units per microg of purified LPS, which was approximately 4,000 times less than Escherichia coli O55:B5 LPS. To determine in vivo endotoxicity, LPS responder mice were administered LPS following galactosamine (GalN) sensitization. The LPS induced neither endotoxic symptoms nor lethality for 96 h, suggesting negligible or very low endotoxicity. In contrast, infection with live T. pectinovorum induced 100% lethality within 12 h in GalN-sensitized LPS responder mice, indicating an endotoxin-like property of this treponeme. Heat-killed microorganisms exhibited no lethality in GalN-sensitized mice, suggesting that the endotoxicity was associated with heat-labile components. To determine cytokine and chemokine induction by LPS, human gingival fibroblasts were stimulated and secretion of interleukin 1beta (IL-1beta), granulocyte-macrophage colony-stimulating factor, gamma interferon, IL-6, IL-8, and monocyte chemoattractant protein 1 (MCP-1) was assessed. The purified LPS induced significant amounts of only IL-6, IL-8, and MCP-1, although they were substantially lower than levels after challenge with live T. pectinovorum. After injection of LPS or live or heat-killed T. pectinovorum, serum was collected from mice and analyzed for proinflammatory cytokines IL-1beta, tumor necrosis factor alpha (TNF-alpha), and IL-6. LPS induced only IL-6 consistently. Both live and heat-killed T. pectinovorum induced serum IL-6, which was higher than the level detected following LPS administration. Importantly, live bacteria elicited systemic TNF-alpha and IL-1beta levels similar to those induced by a lethal dose of live E. coli O111. The results indicated that T. pectinovorum LPS has very low or no endotoxicity, although it can elicit low levels of cytokines from host cells. In contrast to the LPS, live T. pectinovorum demonstrated in vivo toxicity, which was associated with serum IL-1beta, TNF-alpha, and IL-6, suggesting an endotoxin-like property of a heat-labile molecule(s) of the spirochete.
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PMID:Biological characterization of lipopolysaccharide from Treponema pectinovorum. 1174 85

Intratracheal instillation of the monocyte chemoattractant JE/monocyte chemoattractant protein (MCP)-1 in mice was recently shown to cause increased alveolar monocyte accumulation in the absence of lung inflammation, whereas combined JE/MCP-1/lipopolysaccharide (LPS) challenge provoked acute lung inflammation with early alveolar neutrophil and delayed alveolar monocyte influx. We evaluated the role of resident alveolar macrophages (rAM) in these leukocyte recruitment events and related phenomena of lung inflammation. Depletion of rAM by pretreatment of mice with liposomal clodronate did not affect the JE/MCP-1-driven alveolar monocyte accumulation, despite the observation that rAM constitutively expressed the JE/MCP-1 receptor CCR2, as analyzed by flow cytometry and immunohistochemistry. In contrast, depletion of rAM largely suppressed alveolar cytokine release as well as neutrophil and monocyte recruitment profiles upon combined JE/MCP-1/LPS treatment. Despite this strongly attenuated alveolar inflammatory response, increased lung permeability was still observed in rAM-depleted mice undergoing JE/MCP-1/LPS challenge. Lung leakage was abrogated by codepletion of circulating neutrophils or administration of anti-CD18. Collectively, rAM are not involved in JE/MCP-1-driven alveolar monocyte recruitment in noninflamed lungs but largely contribute to the alveolar cytokine response and enhanced early neutrophil and delayed monocyte influx under inflammatory conditions (JE/MCP-1/LPS deposition). Loss of lung barrier function observed under these conditions is rAM independent but involves circulating neutrophils via beta(2)-integrin engagement.
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PMID:Role of resident alveolar macrophages in leukocyte traffic into the alveolar air space of intact mice. 1200 80

Macrophages are numerous in the testicular interstitial tissue under normal conditions and increase during inflammation. The mechanisms involved are poorly characterized. Expression of the macrophage-regulating cytokines monocyte chemoattractant protein (MCP)-1 and macrophage colony-stimulating factor (M-CSF) was examined in the adult rat testis before and after an i.p. injection of an inflammatory stimulus, lipopolysaccharide (LPS). In the normal testis, M-CSF was readily observed using Northern blot and Western blot analysis. In contrast, MCP-1 was not detectable by Northern blot in the normal testis, but was detected using RT-PCR amplification and a sensitive ELISA. After LPS treatment, testicular MCP-1 mRNA and protein expression increased dramatically (up to 400-fold). In-situ hybridization for MCP-1 revealed that production was confined to the interstitium of the inflamed testis, in Leydig cells, peritubular cells, perivascular cells and monocyte-like macrophages, but not in tissue-resident macrophages. Unlike MCP-1, M-CSF mRNA and protein expression in the testis increased only marginally, if at all, after LPS treatment. These results suggest that MCP-1 stimulates the increase in intratesticular macrophages that accompanies LPS-induced inflammation in vivo. Together with M-CSF, MCP-1 may also play a role in maintaining the resident macrophage population of the normal testis.
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PMID:Expression of monocyte chemoattractant protein-1 and macrophage colony-stimulating factor in normal and inflamed rat testis. 1202 68

The interactions of Neisseria meningitidis with cells of the leptomeninges are pivotal events in the progression of bacterial leptomeningitis. An in vitro model based on the culture of human meningioma cells was used to investigate the role of the leptomeninges in the inflammatory response. Following challenge with meningococci, meningioma cells secreted specifically the proinflammatory cytokine interleukin-6 (IL-6), the CXC chemokine IL-8, the CC chemokines monocyte chemoattractant protein 1 (MCP-1) and regulated-upon-activation, normal-T-cell expressed and secreted protein (RANTES), and the cytokine growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). A temporal pattern of cytokine production was observed, with early secretion of IL-6, IL-8, and MCP-1 followed by later increases in RANTES and GM-CSF levels. IL-6 was induced equally by the interactions of piliated and nonpiliated meningococci, whereas lipopolysaccharide (LPS) had a minimal effect, suggesting that other, possibly secreted, bacterial components were responsible. Induction of IL-8 and MCP-1 also did not require adherence of bacteria to meningeal cells, but LPS was implicated. In contrast, efficient stimulation of RANTES by intact meningococci required pilus-mediated adherence, which served to deliver increased local concentrations of LPS onto the surface of meningeal cells. Secretion of GM-CSF was induced by pilus-mediated interactions but did not involve LPS. In addition, capsule expression had a specific inhibitory effect on GM-CSF secretion, which was not observed with IL-6, IL-8, MCP-1, or RANTES. Thus, the data demonstrate that cells of the leptomeninges are not inert but are active participants in the innate host response during leptomeningitis and that there is a complex relationship between expression of meningococcal components and cytokine induction.
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PMID:Interaction of Neisseria meningitidis with human meningeal cells induces the secretion of a distinct group of chemotactic, proinflammatory, and growth-factor cytokines. 1211 9

Alveolar macrophages are likely the first cell type to encounter Mycobacterium tuberculosis in a pulmonary infection, resulting in the production of chemokines. In order to evaluate this response, alveolar macrophages harvested from nonvaccinated and Mycobacterium bovis BCG-vaccinated guinea pigs were infected in vitro with live M. tuberculosis H37Ra or H37Rv (multiplicity of infection, 1:1) or cultured with lipopolysaccharide (10 micro g/ml) for 3, 12, and 24 h. Interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) mRNA expression was determined by real-time PCR. Culture supernatants were assayed for guinea pig IL-8 protein by using a human IL-8 enzyme-linked immunosorbent assay kit. Alveolar macrophages harvested from BCG-vaccinated guinea pigs produced significantly more mRNA and protein for IL-8 than alveolar macrophages harvested from nonvaccinated guinea pigs at 12 and 24 h poststimulation or postinfection. Infection with attenuated M. tuberculosis (H37Ra) stimulated alveolar macrophages isolated from BCG-vaccinated guinea pigs to produce significantly more IL-8 mRNA than did alveolar macrophages infected with a virulent strain (H37Rv) at 12 and 24 h postinfection. Significant MCP-1 mRNA production was also detected in stimulated or infected alveolar macrophages; however, prior vaccination did not significantly affect levels of MCP-1 mRNA. Alveolar macrophages isolated from BCG-vaccinated guinea pigs produced significantly more IL-8 mRNA and protein when stimulated for 24 h with heat-killed H37Ra, heat-killed H37Rv, and H37Rv cell wall, but not mannose-capped lipoarabinomannan (ManLAM), than did cells stimulated with media alone. These observations indicate that prior vaccination may alter very early events in the M. tuberculosis-infected lung.
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PMID:Mycobacterium bovis BCG vaccination augments interleukin-8 mRNA expression and protein production in guinea pig alveolar macrophages infected with Mycobacterium tuberculosis. 1222 72

We have previously reported that differences in early production of interleukin 12 (IL-12) by dendritic cells (DC) underlies the difference between the susceptibilities to Listeria monocytogenes of C57BL/6 and BALB/c mice. To elucidate mechanisms for the different abilities of DC to produce cytokine in C57BL/6 and BALB/c mice, we examined Toll-like receptor (TLR) expression by DC and their responses in vitro to known microbial ligands for TLRs. We found that DC isolated from the spleens of naive C57BL/6 mice preferentially expressed TLR9 mRNA, whereas DC from naive BALB/c mice strongly expressed TLR2, -4, -5, and -6 mRNAs. C57BL/6 DC produced a higher level of IL-12p40 in response to the ligands for TLR4 (lipopolysaccharide), TLR2 (lipoprotein), and TLR9 (CpG), whereas BALB/c DC responded to these ligands by producing a larger amount of monocyte chemoattractant protein 1. C57BL/6 DC expressed higher levels of CD40 and Stat4 than BALB/c DC did, suggesting that naive C57BL/6 mice contained more-mature subsets of DC than naive BALB/c mice. Differences in reactivities of DC to microbial molecules through TLRs may be associated with susceptibility and resistance to Listeria infection in BALB/c and C57BL/6 mice.
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PMID:Differences in expression of toll-like receptors and their reactivities in dendritic cells in BALB/c and C57BL/6 mice. 1243 36


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