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

T-lymphocytes (LYs) from normal and IFN-gamma knockout mice were activated by anti-CD3 and anti-CD28 antibodies and cultured in inserts in the presence of interleukin (IL)-12 (IL-12-activated LYs) or not (activated LYs). Their ability to modulate the genetic programs of two tumor lines growing at the bottom of transwells was evaluated. cDNA gene expression array, reverse transcription-PCR, and protein expression showed that LPS, transcription termination factor 1, transforming growth factor, and fibroblast growth factor genes were up-modulated by factors other than IFN-gamma released by activated LYS: The high levels of IFN-gamma released by normal IL-12-activated LYs up-modulated the expression of STAT1, IRF-1, LMP2, LMP7, monokine induced by IFN-gamma, monocyte chemoattractant protein 1, and angiopoietin 2 genes but down-modulated the expression of vascular endothelial growth factor. PA28, IFN-inducible protein 10, inducible NO synthetase, and macrophage-inhibitory protein 2 genes were up-modulated by factors released only by IL-12-activated LYs apart from IFN-gamma. The opposite modulations of vascular endothelial growth factor expression and of angiopoietin 2, monokine induced by IFN-gamma, IFN-inducible protein 10, and inducible NO synthetase by IL-12-activated LYs fit in well with the inhibition of angiogenesis that characterizes the antitumor activity of IL-12. T-LYs thus modify a tumor's behavior so that it becomes a party to its own inhibition.
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PMID:Interleukin 12-activated lymphocytes influence tumor genetic programs. 1130 16

Adenosine has been implicated as a modulator of inflammatory processes central to asthma. However, the molecular mechanisms involved are poorly understood. We used Atlas mouse cDNA arrays to analyze differential gene expression in association with lung inflammation resulting from elevated adenosine in adenosine deaminase (ADA)-deficient mice. We report that of the 1,176 genes on the array, the expression patterns of 280 genes were consistently altered. Of these genes, the steady-state levels of 93 genes were upregulated and 29 were downregulated. We also show that lowering adenosine levels with ADA enzyme therapy has striking effects on gene expression that may be associated with resolution of pulmonary eosinophilia. In addition, we confirmed the nucleic acid and protein expression of vascular endothelial growth factor and monocyte chemoattractant protein-3, two candidate genes that may be regulated by adenosine. In conclusion, high-throughput profiling of gene expression by cDNA array hybridization has provided an overview of critical regulatory genes involved in airway inflammation in ADA-deficient mice. These mice will serve as a useful in vivo model for characterizing molecular mechanisms of adenosine-mediated lung damage.
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PMID:Gene expression profiling in inflammatory airway disease associated with elevated adenosine. 1179 19

To clarify biological roles of tumor necrosis factor receptor p55 (TNF-Rp55) -mediated signals in wound healing, skin excisions were prepared in BALB/c (WT) and TNF-Rp55-deficient (KO) mice. In WT mice, the wound area was reduced to 50% of the original area 6 days after injury, with angiogenesis and collagen accumulation. Histopathologically, reepithelialization rate was approximately 80% 6 days. Myeloperoxidase activity and macrophage recruitment were the most evident 1 and 6 days after injury, respectively. Gene expression of adhesion molecules, interleukin 1alpha (IL-1alpha), IL-1beta, monocyte chemoattractant protein 1, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-2, transforming growth factor beta1 (TGF-beta1) connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), Flt-1, and Flk-1 was enhanced at the wound site. In KO mice, an enhancement in angiogenesis, collagen content, and reepithelialization was accelerated with the increased gene expression of TGF-beta1, CTGF, VEGF, Flt-1, and Flk-1 at the wound sites, resulting in accelerated wound healing compared with WT mice. In contrast, leukocyte infiltration, mRNA expression of adhesion molecules, and cytokines were significantly reduced in KO mice. These observations suggest that TNF-Rp55-mediated signals have some role in promoting leukocyte infiltration at the wound site and negatively affect wound healing, probably by reducing angiogenesis and collagen accumulation.
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PMID:Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration. 1208 57

LH and PGF(2alpha) are the principal luteotrophic and luteolytic hormones in domestic animals, however, it is becoming increasingly apparent that intra-ovarian factors can modulate luteal function. For example, the insulin-like growth factors (IGF-I and -II) can regulate ovarian function, and have direct effects on ovarian cells. An important role for the IGFs in regulating ovarian function is suggested by the multiple effects of IGFs on both follicular and luteal steroidogenesis. Expression of mRNA encoding IGF-I, IGF-II and the type 1 IGF receptor has also been detected in the ruminant CL and is suggestive of autocrine/paracrine roles for both IGF-I and -II in the regulation of luteal function. The actions of the IGFs are further modulated by their association with specific binding proteins (IGFBPs), which regulate the transport of IGFs and their presentation to specific receptors. IGFBPs have been detected in the CL of domestic animals, and inhibitory effects on IGF-I-stimulated progesterone production have been demonstrated. The rapid cyclical changes in luteal growth and regression are associated with rapid changes in vasculature. The principle angiogenic factors include the fibroblast growth factors (FGFs), vascular endothelial growth factor (VEGF) and the angiopoietins (Ang). Other locally produced factors include cytokines such as TNF-alpha and IL-1beta. One such factor is monocyte chemoattractant protein (MCP-1), which increases after exogenous PGF(2alpha). An influx of macrophages takes place in the CL around luteolysis, possibly in response to MCP-1 release, but these changes are not observed in cattle when luteolysis is inhibited. In conclusion locally produced factors are important in the control of luteal function, although their roles have yet to fully elucidated.
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PMID:Corpus luteum (CL) function: local control mechanisms. 1214 44

Tumor angiogenesis requires the production of angiogenic factors by tumor and stromal cells. Macrophages are key effectors of angiogenesis and reported to contribute to tumor angiogenesis in several carcinomas. To investigate interactions between tumor cells and macrophages in angiogenesis, we examined macrophage infiltration, tumor vascularity and expression of monocyte chemoattractant protein (MCP)-1, CC chemokine receptor 2 (CCR2) and vascular endothelial growth factor (VEGF) in 57 archival specimens from patients with esophageal dysplasia (n = 9) and squamous cell carcinomas (n = 48). Expression of MCP-1 mRNA was also examined by reverse transcriptase-polymerase chain reaction (RT-PCR) in 7 esophageal carcinoma cell lines and fresh biopsy specimens from 14 patients. The number of infiltrating macrophages correlated closely with expression of VEGF by tumor cells and with neovascularization. Of the 7 cell lines, 4 (TE-1, 3, 5 and 13) constitutively expressed MCP-1 mRNA. In 9 (64.3%) of the 14 patients, MCP-1 mRNA was expressed at high levels in tumor tissues as compared to normal mucosa. MCP-1 immunoreactivity increased with the depth of tumor invasion (Tis 0%, T1 26.3%, T2, T3 42.1%). Moreover, macrophage and vessel counts were significantly higher in MCP-1-positive tumors than in MCP-1-negative tumors. Normal and dysplastic esophageal squamous epithelium showed no staining or faint cytoplasmic staining of MCP-1. Expression of CCR2 immunoreactivity was detected in the cytoplasm of mononuclear cells but not of vascular endothelial cells. These results suggest that interactions between cancer cells and macrophages are important for tumor angiogenesis. MCP-1 may play a role in progression of human esophageal carcinoma through its role in angiogenesis.
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PMID:Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human esophageal squamous cell carcinomas. 1239 39

To characterize the roles of Porphyromonas gingivalis and its components in the disease processes, we investigated the cytokine profile induced by live P. gingivalis, its lipopolysaccharides (LPS), and its major fimbrial protein, fimbrillin (FimA). Using cytokine antibody arrays, we found that P. gingivalis LPS and FimA induced a similar profile of cytokine expression when exposed to mouse peritoneal macrophages but that this profile differed significantly in response to live P. gingivalis. In vitro, mouse peritoneal macrophages were stimulated to produce interleukin-6 (IL-6), granulocyte colony-stimulating factor, and lymphotactin by live P. gingivalis, but not by P. gingivalis LPS or FimA, while RANTES, gamma interferon, IL-17, vascular cell adhesion molecule 1 (VCAM-1), and vascular endothelial growth factor were induced by P. gingivalis LPS or FimA, but not by live P. gingivalis. In vivo, IL-6 mRNA was strongly induced only by live P. gingivalis while monocyte chemoattractant protein 1 mRNA was strongly induced only by P. gingivalis LPS and FimA in mouse calvarial scalp, further confirming the differences of cytokine profile induced in vitro. Cytokine antibody arrays using toll-like receptor 2 (TLR2)- and TLR4-deficient macrophages revealed that most of the cytokines induced by P. gingivalis LPS or FimA signal through TLR2, while most of cytokines induced by live P. gingivalis signal through both TLR2 and TLR4. Interestingly, the activation of TLR2 by live P. gingivalis inhibited the release of RANTES, VCAM-1, and IL-1alpha from mouse peritoneal macrophages. A tumor necrosis factor alpha enzyme-linked immunosorbent assay further confirmed that P. gingivalis LPS and FimA activate mouse peritoneal macrophages via TLR2. These results indicate that host immune cells sense live P. gingivalis and its components differently, which translates into the expression of different inflammatory cytokine profiles.
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PMID:Cytokine profiling of macrophages exposed to Porphyromonas gingivalis, its lipopolysaccharide, or its FimA protein. 1566 35

Seventy-nine cytokines, chemokines, and growth factors were measured by protein array analysis in the cerebrospinal fluid of patients with meningitis and controls. Several factors were found to be regulated, which have not been studied in the CNS before, e.g., macrophage inflammatory protein-1delta (CCL15) and neutrophil-activating peptide-2 (CXCL7). In pneumococcal meningitis, other new observations were an increase of macrophage migration inhibitory factor, monocyte chemoattractant protein-2 (CCL8), pulmonary and activation-regulated chemokine (CCL18), and macrophage inflammatory protein-3alpha (CCL20), and a sustained upregulation of several growth factors. In viral meningitis, new findings were an elevation of CCL8, thrombopoietin, and vascular endothelial growth factor.
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PMID:Patterns of protein expression in infectious meningitis: a cerebrospinal fluid protein array analysis. 1588 8

Leptin upregulates collagen expression in hepatic stellate cells (HSCs), but the possible modulation of other actions has not been elucidated. The aim of this study was to investigate the expression and function of leptin receptors (ObR) in human HSCs and the biological actions regulated by leptin. Exposure of HSCs to leptin resulted in upregulation of monocyte chemoattractant protein 1 (MCP-1) expression. Leptin also increased gene expression of the proangiogenic cytokines vascular endothelial growth factor (VEGF) and angiopoietin-1, and VEGF was also upregulated at the protein level. Activated HSCs express ObRb and possibly other ObR isoforms. Exposure to leptin increased the tyrosine kinase activity of ObR immunoprecipitates and resulted in activation of signal transducer and activator of transcription 3. Several signaling pathways were activated by leptin in HSCs, including extracellular-signal-regulated kinase, Akt, and nuclear factor kappaB, the latter being relevant for chemokine expression. Leptin also increased the abundance of hypoxia-inducible factor 1alpha, which regulates angiogenic gene expression, in an extracellular-signal-regulated kinase- and phoshatidylinositol 3-kinase-dependent fashion. In vivo, leptin administration induced higher MCP-1 expression and more severe inflammation in mice after acute liver injury. Conversely, in leptin-deficient mice, the increase in MCP-1 messenger RNA and mononuclear infiltration was less marked than in wild-type littermates. Finally, ObR expression colocalized with VEGF and alpha-smooth muscle actin after induction of fibrosis in rats. In conclusion, ObR activation in HSCs leads to increased expression of proinflammatory and proangiogenic cytokines, indicating a complex role for leptin in the regulation of the liver wound-healing response.
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PMID:Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. 1631 88

The Fas-Fas ligand interaction is the most important pathway in starting apoptosis. In addition, several recent reports have emerged documenting non-apoptotic roles for Fas. However, a non-apoptotic role of Fas in dermal fibroblasts remains unknown. The present study investigated whether Fas stimulation not only promotes apoptosis but also stimulates elements of the inflammatory response such as angiogenesis and macrophage infiltration. Fas stimulation was performed by treating cultured human dermal fibroblasts with an agonistic anti-Fas monoclonal antibody (mAb). Anti-Fas mAb-treated fibroblasts showed a significantly greater increase of caspase-3 and caspase-8 activity compared with control fibroblasts. Addition of the anti-Fas mAb induced DNA fragmentation, as confirmed by the DNA ladder assay. Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) staining showed that treatment with the anti-Fas mAb induced an increase of apoptotic fibroblasts in a time-dependent manner. At both mRNA and protein levels, anti-Fas mAb-treated fibroblasts showed significantly higher expression of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP)-1 compared with control fibroblasts. A pan-caspase inhibitor (Z-VAD-FMK) significantly inhibited VEGF and MCP-1 expression. After transplantation of fibroblasts into mice with severe combined immunodeficiency, the nodules derived from anti-Fas mAb-treated fibroblasts showed more abundant neovascularization, increased macrophage infiltration, and more apoptotic cells in comparison with nodules derived from control fibroblasts. The results of both in vitro and in vivo studies confirmed significantly higher angiogenic activity and macrophage chemotactic activity of anti-Fas mAb-treated fibroblasts compared with control fibroblasts.
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PMID:Fas-mediated upregulation of vascular endothelial growth factor and monocyte chemoattractant protein-1 expression in cultured dermal fibroblasts: role in the inflammatory response. 1723 46

The bacterial single cell protein (BSCP), BioProtein, is dried bacterial mass derived from fermentation of the gram negative bacteria Methylococcus capsulatus, used for animal and fish feed. Workers in this industry suffer frequently from pulmonary and systemic symptoms which may be induced by an inflammatory reaction. The aim of the present study was to examine the effect of BSCP on inflammation in vitro as evaluated by complement activation and cytokine production. Human serum was incubated with BSCP and complement activation products specific for all pathways were detected by enzyme-linked immunosorbent assay (ELISA). Human whole blood anti-coagulated with lepirudin was incubated with BSCP and a panel of 27 biological mediators was measured using multiplex technology. BSCP induced a dose-dependent complement activation as revealed by a pronounced increase in alternative and terminal pathway activation (fivefold and 20-fold, respectively) at doses from 1 microg BSCP/ml serum and a similar, but less extensive (two- to fourfold) increase in activation of the lectin and classical pathways at doses from 100 and 1000 microg BSCP/ml serum, respectively. Similarly, BSCP induced a dose-dependent production of a number of cytokines, chemokines and growth factors in human whole blood. At doses as low as 0 x 05-0 x 5 microg BSCP/ml blood a substantial increase was seen for tumour necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, IL-6, interferon (IFN)-gamma, IL-8, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, IL-4, IL-9, IL-17, IL-1Ra, granulocyte-colony-stimulating factor (G-CSF) and vascular endothelial growth factor (VEGF). Thus, BSCP induced a substantial activation of all three initial complement pathways as well as a pronounced cytokine response in vitro, indicating a potent inflammatory property of this agent.
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PMID:Complement activation and cytokine response by BioProtein, a bacterial single cell protein. 1730 29


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