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)

Previous studies have shown that engagement of Toll-like receptors (TLR) 2 and 4 can induce macrophages to express a variety of proinflammatory cytokines. We have recently demonstrated that TLR2 agonists poorly induce a subset of TLR4-inducible proinflammatory genes (e.g., inducible protein (IP)-10, inducible NO synthase (iNOS), monocyte chemoattractant protein-5, IL-12p40), due in part to differential activation of IFN-beta production and phosphorylation of the transcription factor STAT1. TLR4, but not TLR2, agonists can induce IFN-beta expression via a mechanism that requires the adapter protein Toll-IL-1R domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 (MyD88) adapter-like (Mal), but not the adapter protein MyD88. Thus, the failure of TLR2 agonists to induce STAT1-dependent genes results, in part, from their failure to induce the expression of IFN-beta. In this study, we show that IL-6 expression is also preferentially induced by activation of TLR4. TLR4-dependent induction of IL-6 expression did require Toll-IL-1R domain-containing adapter protein (TIRAP)/MyD88 adapter-like (Mal), but unlike iNOS and IP-10, it did not require the expression of IFN-beta. Although exogenous IFN-beta and IFN-gamma could synergize with TLR2 agonists to restore high levels of iNOS expression and NO production, these IFNs could not synergize with TLR2 agonists to induce high levels of IL-6. Similarly, neutralizing anti-IFN Abs could block iNOS gene expression in LPS-stimulated murine macrophages, whereas these Abs had little effect on IL-6 gene expression in these cells. Together, these studies demonstrate that IL-6, like iNOS and IP-10, is differentially expressed in macrophages stimulated via TLR2 vs TLR4, although these differences appear to arise from distinct signaling mechanisms.
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PMID:Toll-like receptor 4 and Toll-IL-1 receptor domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 adapter-like (Mal) contribute to maximal IL-6 expression in macrophages. 1242 70

The high-affinity receptor for IgE, FcepsilonRI, on APCs plays an important role in the initiation and chronicity of inflammatory atopic diseases. To understand the molecular regulation of FcepsilonRI-mediated processes, differentially expressed genes are of great interest to be identified. Suppression subtractive cDNA hybridization has been used to identify genes induced after FcepsilonRI stimulation on atopic monocytes. Overexpression of the identified genes was determined by semiquantitative RT-PCR analysis of transcripts from the tester (stimulated) and driver (unstimulated) monocytes. Results were confirmed and kinetics of the transcripts established using blood cells from additional atopics at 4 and 24 h of FcepsilonRI induction. The following sequences were identified: monocyte chemoattractant protein 1, macrophage-inflammatory protein 1beta, IL-6, beta(A) subunit of inhibin/activin, IFN-stimulated gene of 54 kDa, IL-1R antagonist, and kynurenine 3-monooxygenase. Chemokines are highly expressed during the early and late phase after FcepsilonRI cross-linking, whereas proinflammatory and differentiation stimuli rapidly decline after an initial overexpression. Kynurenine 3-monooxygenase, an enzyme involved in the degradation of the amino acid tryptophan, is significantly up-regulated during the late phase after 24 h of FcepsilonRI induction. These results demonstrate that the analysis of the profile of gene induction following activation of FcepsilonRI on atopic monocytes may reveal how these cells might participate in the regulation of atopic disorders.
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PMID:Kinetics of gene induction after FcepsilonRI ligation of atopic monocytes identified by suppression subtractive hybridization. 1244 21

Human T-cell leukemia virus type I (HTLV-I) provirus load differs more than 100-fold among carriers and a high provirus load in the peripheral blood mononuclear cells (PBMCs) is regarded as a risk factor for both preleukemic states and inflammatory diseases including HTLV-I-associated myelopathy (HAM). We examined polymorphisms in the genes for tumor necrosis factor (TNF), TNF receptor type 1 and 2, lymphotoxin (LT)-alpha, interleukin (IL)-1beta, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and mannose binding protein (ManBP) in 143 HTLV-I carriers whether these polymorphisms affect the provirus load in the PBMCs of carriers. No significant association was observed between these polymorphisms and the provirus load. Homozygotes for a ManBP-variant allele, however, showed a tendency for the decreased number of provirus load. When combined, the data on the alleles of LT-alpha and MCP-1, HTLV-I carriers having high producer alleles of both genes showed a trend for increased provirus load. These data suggest that inflammation or an active immune response may induce an increased amount of HTLV-I-infected T cells, leading to a high provirus load.
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PMID:Influence of cytokine and mannose binding protein gene polymorphisms on human T-cell leukemia virus type I (hTLV-I) provirus load in HTLV-I asymptomatic carriers. 1265 Oct 71

Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell-cell and cell-extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-beta]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-alpha in the presence of different concentrations (0.01-100.0nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF (p<0.05), whereas TNF-alpha induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (p<0.05, each comparison). No changes in HCAM expression and in TGF-beta release were observed (p>0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release (p<0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release (p<0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-beta release (p>0.05, each comparisons). These results extend the profile of the anti-inflammatory activity of mometasone furoate to lung fibroblast functions involved in airway inflammation and remodeling.
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PMID:Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling. 1287 20

In this study, we demonstrate that Dermatophagoides farinae (Der f), a major source of airborne allergens, but not OVA, could rapidly activate mast cells in mice. This was indicated by an elevation of serum mouse mast cell protease 1, a mast cell-specific proteinase, as early as 30 min after intratracheal challenge. Administration of sodium cromoglycate (40 mg/kg, i.p., 1 h before Der f instillation), a mast cell stabilizer, not only suppressed acute mouse mast cell protease 1 production but also attenuated the allergic airway inflammation provoked by repetitive Der f challenge in mice (five times at 1-wk interval). Der f induced the expression of mRNA for TNF-alpha, IL-1beta, IL-4, IL-6, IL-9, and IL-13 in mastocytoma P815 cells and stimulated both P815 cells and bone marrow-derived mast cells to produce IL-4, IL-6, and TNF-alpha in a dose- and time-dependent manner. Cycloheximide as well as sodium cromoglycate blocked the Der f-induced IL-4 production, indicating a de novo protein synthesis process. Supernatants of Der f-stimulated mast cells chemoattracted monocytes and T lymphocytes; they up-regulated the expression of costimulatory B7 molecules, eotaxin, RANTES, monocyte chemoattractant protein 1, and IFN-inducible protein 10 mRNA of alveolar macrophages; they supported PHA-induced T cell proliferation; and they promoted Th2 cell development. Our data indicate that mast cells may be an important cell type during the initiation of Der f sensitization in the airway by modulating the function of alveolar macrophages and T cells.
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PMID:Activation of mast cells is essential for development of house dust mite Dermatophagoides farinae-induced allergic airway inflammation in mice. 1450 Jun 82

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

Small volumes of cervical secretions have limited measurements of immunity at the cervix, which may be important to studies of human papillomavirus (HPV). We report the use of recycling immunoaffinity chromatography to efficiently study immune profiles in cervical secretions. Frozen pairs of plasma and cervical secretions (collected on ophthalmic sponges) were selected randomly from women with normal cervical cytology (n = 50) participating in a natural history study of HPV in Guanacaste, Costa Rica. Single 25- micro l aliquots of plasma and (diluted) cervical secretions were assayed for interleukin (IL) -1 beta, -2, -4, -6, -8, -10, -12, -13, -15, IFN-alpha, -beta, -gamma, tumor necrosis factor-alpha, -beta, RANTES (regulated on activation normal T-cell express and secreted), MCP-1 (monocyte chemoattractant protein), -2, -3, macrophage inflammatory protein-1 alpha, -1 beta (regulated on activation normal T-cell express and secreted), macrophage colony-stimulating factor, IgG, IgA, and cyclooxygenase 2. All of the specimens were tested as blind replicates, and refrozen plasma was retested 4 months later. To evaluate the reproducibility of the repeat measurements and to examine the correlation between plasma and cervical secretions, we calculated kappa values with 95% confidence intervals among categorized analyte values and Spearman correlation coefficients (rho) among detectable, continuous analyte values. Measurements of all of the analytes in either plasma or cervical secretions were highly reproducible, with all of the kappa > or = 0.78 (70% above 0.90), and all of the rho > or = 0.88 (96% above 0.90). Only IL-1 beta (kappa = 0.60 and rho = 0.82) and IL-6 (kappa = 0.50 and rho = 0.78) levels were strongly correlated between plasma and cervical secretions. IFN-gamma, tumor necrosis factor-beta, RANTES, MCP-1, MCP -2, macrophage inflammatory protein-1 alpha, and macrophage colony-stimulating factor levels were especially poorly correlated between plasma and cervical secretions (kappa < or = 0.25 and rho < or = 0.25). We conclude that recycling immunoaffinity chromatography is a reproducible method of measuring immune profiles from biological specimens, and immune profiles are not well correlated between plasma and cervical secretions, perhaps necessitating cervical collections to study cervix-specific immunity in HPV natural history studies.
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PMID:Immune profiling of plasma and cervical secretions using recycling immunoaffinity chromatography. 1469 36

During the last 10 years, various adipocytokines have been described which influence insulin sensitivity profoundly and might, therefore, potentially link obesity and insulin resistance. Recently, monocyte chemoattractant protein (MCP)-1 was characterized as a novel adipose-secreted factor upregulated in obesity and insulin resistance that impairs insulin signaling in fat cells in vitro and can be found in atherosclerotic lesions. To clarify expression and regulation of this adipocytokine, MCP-1 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance. Interestingly, MCP-1 synthesis was significantly downregulated between 43% and 68% during differentiation of 3T3-L1 preadipocytes. Furthermore, 10 ng/ml tumor necrosis factor alpha, 100 nM insulin, 500 ng/ml growth hormone (GH), and 30 ng/ml interleukin (IL)-6-induced MCP-1 mRNA by up to 124-, 23-, 8-, and 2.5-fold, respectively, in a time-dependent fashion with significant stimulation seen at concentrations as low as 0.5 ng/ml GH and 30 ng/ml IL-6. In contrast, the glucocorticoid dexamethasone potently downregulated MCP-1 with significant suppression detectable at concentrations as low as 3 nM and as early as 2h after effector addition. Studies using pharmacological inhibitors suggested that the positive effects of GH and IL-6 on MCP-1 synthesis are at least in part mediated by janus kinase 2 and p44/42 mitogen-activated protein kinase. Taken together, our results show a differential regulation of MCP-1 mRNA by insulin resistance-inducing hormones and support the view that this adipocytokine might be an interesting novel candidate linking insulin resistance, obesity, and atherosclerosis. This adipocytokine could thus be a potential pharmacological target for the treatment of impaired insulin sensitivity.
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PMID:Monocyte chemoattractant protein 1 expression is stimulated by growth hormone and interleukin-6 in 3T3-L1 adipocytes. 1506 99

Avenanthramides are phenolic antioxidants, which are present in oats. Avenanthramides A, B, and C are the major constituents of the total soluble antioxidant phenolic compounds in oats. We tested the potential antiatherogenic activity of partially purified avenanthramides from oats by examining their effects on adhesion of monocytes to human aortic endothelial cell (HAEC) monolayers, expression of adhesion molecules, and production of proinflammatory cytokines and chemokines by HAEC. The oat avenanthramides mixture was prepared and partially purified by column chromatography. This avenanthramide-enriched mixture (AEM) had no toxicity to HAEC as tested up to 40 ng/ml. The pre-incubation of HAEC with 4, 20, and 40ng/ml AEM for 24h significantly decreased adhesion of U937 monocytic cells to interleukin (IL)-1beta-stimulated HAEC in a concentration-dependent manner. Pre-incubation of HAEC with AEM at 20 and 40 microg/ml, but not at 4 microg/ml, for 24h significantly suppressed IL-1beta-stimulated expressions of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin and the secretion of proinflammatory cytokines IL-6, chemokines IL-8 and monocyte chemoattractant protein (MCP)-1. These data provide evidence for the potential anti-inflammatory and antiatherogenic effects of antioxidant avenanthramides present in oats.
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PMID:The antiatherogenic potential of oat phenolic compounds. 1518 45

Calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid or urate are the most common crystals seen in the kidneys. Most of the crystals evoke an inflammatory response leading to fibrosis, loss of nephrons, and eventually to chronic renal failure. Of the three, CaOx monohydrate is the most reactive, whereas some forms of CaP do not evoke any discernible response. Reactive oxygen species are produced during the interactions between the crystals and renal cells and are responsible for the various cellular responses. CaOx crystals generally form in the renal tubules. Exposure of renal epithelial cells to CaOx crystals results in the increased synthesis of osteopontin, bikunin, heparan sulfate, monocyte chemoattractant protein 1 (MCP-1), and prostaglandin (PG) E2, which are known to participate in inflammatory processes and in extracellular matrix production. CaOx crystal deposition in rat kidneys also activates the renin-angiotensin system. Both Ox and CaOx crystals selectively activate p38 mitogen-activated protein kinase (MAPK) in exposed tubular cells. CaP crystals can form in the tubular lumen, tubular cells, or tubular basement membrane. Renal epithelial cells exposed to brushite crystals produce MCP-1. Basic CaP and calcium pyrophosphate dihydrate induce mitogenesis in fibroblasts, stimulate production of PGE2, and up-regulate the synthesis of metalloproteinases (MMP) while down-regulating the production of inhibitors of MMPs through activation of p42/44 MAPK. Deposition of urate crystals in the kidneys becomes associated with renal tubular atrophy, interstitial fibrosis, and development of inflammatory infiltrate. Renal epithelial cells exposed to uric acid crystals synthesize MCP-1 as well as PGE2. Monocytes or neutrophils exposed to urate crystals produce tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6, and IL-8. Expression of IL-8 is mediated through extracellular signal-regulated kinase 1 (ERK-1)/ERK-2 and nuclear transcription factors activated protein 1 and nuclear factor kappabeta. Urate crystals also stimulate the macrophages to produce MMPs.
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PMID:Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies. 1523 23


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