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)

Lung ischemia-reperfusion (I/R) injury is a biphasic inflammatory process. Previous studies indicate that the later phase is neutrophil-dependent and that alveolar macrophages (AMs) likely contribute to the acute phase of lung I/R injury. However, the mechanism is unclear. AMs become activated and produce various cytokines and chemokines in many inflammatory responses, including transplantation. We hypothesize that AMs respond to I/R by producing key cytokines and chemokines and that depletion of AMs would reduce cytokine/chemokine expression and lung injury after I/R. To test this, using a buffer-perfused, isolated mouse lung model, we studied the impact of AM depletion by liposome-clodronate on I/R-induced lung dysfunction/injury and expression of cytokines/chemokines. I/R caused a significant increase in pulmonary artery pressure, wet-to-dry weight ratio, vascular permeability, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-2 expression, as well as decreased pulmonary compliance, when compared with sham lungs. After AM depletion, the changes in each of these parameters between I/R and sham groups were significantly attenuated. Thus AM depletion protects the lungs from I/R-induced dysfunction and injury and significantly reduces cytokine/chemokine production. Protein expression of TNF-alpha and MCP-1 are positively correlated to I/R-induced lung injury, and AMs are a major producer/initiator of TNF-alpha, MCP-1, and MIP-2. We conclude that AMs are an essential player in the initiation of acute lung I/R injury.
Am J Physiol Lung Cell Mol Physiol 2006 Nov
PMID:Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury. 1686 85

TFII-I is a founding member of a family of helix-loop-helix transcription factors involved in modulation of genes through interaction with various nuclear factors and chromatin remodeling complexes. Recent studies indicate that TFII-I performs important function in cell physiology and mouse embryogenesis. In order to understand its molecular role, TFII-I was overexpressed in primary mouse embryonic fibroblasts (MEFs) and alterations in gene expression were monitored with a mouse 16 K oligonucleotide microarray. These studies allowed us to identify genes that lie downstream of TFII-I-dependent pathways. Among the modulated candidates were genes involved in the immunity response, catalytic activity, signaling pathways and transcriptional regulation. Expression of several candidates including those for the interferon-stimulated protein (G1p2), small inducible cytokine A7 (Ccl7), ubiquitin-conjugating enzyme 8 (Ube2l6), cysteine-rich protein (Csrp2) and Drosophila delta-like 1 homolog (Dlk1) were confirmed by real-time PCR. The obtained results suggest that TFII-I participates in multiple signaling and regulatory pathways in MEFs.
J Exp Zool B Mol Dev Evol 2007 May 15
PMID:Gene expression analysis of TFII-I modulated genes in mouse embryonic fibroblasts. 1709 79

The aim of the current study was to elucidate the potential therapeutic effect of Ganoderma lucidum polysaccharide peptide (GL-PP) in rheumatoid arthritis (RA). The effects of GL-PP on cell proliferation and cytokine production were studied in RA synovial fibroblasts (RASF). GL-PP significantly inhibited the proliferation of RASF. Following the incubation with GL-PP, production of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 in RASF were significantly increased as expressed as percentage change from basal values. However, the actual effects were minimal due to the low basal values. When RASF were activated by IL-1beta or lipopolysaccharides, IL-8 and MCP-1 production increased many folds. GL-PP significantly suppressed their productions. The inhibitory effects of GL-PP on cytokine production in RASF were at least in part, by inhibiting the nuclear factor-kappa B (NF-kappaB) transcription pathway. Our results demonstrated that GL-PP had the unique ability to modulate cytokine production in RASF and warrants further investigation into its mechanism of action.
Mol Cell Biochem 2007 Jul
PMID:Ganoderma lucidum polysaccharide peptide reduced the production of proinflammatory cytokines in activated rheumatoid synovial fibroblast. 1721 61

The majority of primary central nervous system lymphomas (PCNSL) are diffuse large B-cell lymphomas. Histologically, reactive T lymphocytes and mono-histiocytic cells are found within PCNSL tissue. To clarify the mechanisms of the cellular infiltration, the presence of monocyte chemoattractant protein (MCP-1) was investigated in biopsy samples of 19 cases of PCNSL by means of immunohistochemical staining, double staining with a confocal laser microscope, and Western blot analysis. MCP-1 expression was observed in all PCNSL immunohistochemically. Western blot analysis showed that the concentration of MCP-1 in PCNSL was as high as that in a metastatic brain tumor. In normal brain tissue, MCP-1 was not detected. Confocal laser microscope revealed MCP-1 signals were present in the cells with CD20, a B-cell marker. We concluded that lymphoma cells produced MCP-1, which is an additional cytokine involved in the pathogenesis of PCNSL.
Med Mol Morphol 2007 Mar
PMID:Primary central nervous system lymphoma secretes monocyte chemoattractant protein 1. 1738 85

Interleukin (IL)-31 is mainly produced by CD4+ T cells, in particular T cells skewed toward a Th2 phenotype. Here we report for the first time that IL-31 stimulates secretion of proinflammatory cytokines, chemokines and matrix metalloproteinases (MMPs) from human colonic subepithelial myofibroblasts (SEMFs). The effects of IL-31 were investigated by cDNA microarrays, enzyme-linked immunosorbent assay, and real-time PCR. IL-31 effectively induced chemokines [IL-8, GRO-alpha (growth-related oncogene-alpha), MCP-3 (monocyte chemoattractant protein-3), CXCL3, CCL13 and CCL15], proinflammatory cytokines (IL-6, IL-16 and IL-32) and matrix metalloproteinases (MMP-1, MMP-3, MMP-25 and MMP-7). IL-31 dose-dependently induced secretion of IL-6, IL-8, GRO-alpha, MCP-3, MMP-1 and MMP-3. The effects of IL-31 were comparable to the effects of IL-17A. IL-31 and IL-17A showed additive effects on IL-6, IL-8, GRO-alpha, MCP-3, MMP-1 and MMP-3 secretion. In conclusion, we demonstrated that IL-31 is a potent inducer of proinflammatory mediators in human colonic SEMFs. IL-31 may function as a proinflammatory cytokine derived from Th2 cells.
Int J Mol Med 2007 Jun
PMID:Interleukin-31 stimulates production of inflammatory mediators from human colonic subepithelial myofibroblasts. 1748 27

Tumor necrosis factor (TNF)-alpha is a cytokine produced by alveolar macrophages in response to LPS in the lung. Clara cells are bronchiolar epithelial cells that produce a variety of proinflammatory cytokines in response to LPS but not to TNF-alpha. In this study, we examined whether TNF-alpha affects Clara cell cytokine production in the setting of LPS stimulation. Using a transformed murine Clara cell line (C22), we observed that both LPS and TNF-alpha induced production of keratinocyte-derived chemokine (KC) and monocyte chemoattractant protein (MCP)-1. We also found that simultaneous LPS and TNF-alpha stimulation is synergistic for KC production, but additive for MCP-1 production. By using a Transwell coculture system of RAW264.7 macrophages and Clara cells isolated from C57Bl/6 mice, we found that macrophages produce a soluble factor that enhances Clara cell KC production in response to LPS. Cocultures of Clara cells from mice deficient in TNF-alpha receptors with RAW264.7 macrophages demonstrated that the effect of macrophages on Clara cells is mediated primarily via TNF-alpha. To determine whether these findings occur in vivo, we treated wild-type and TNF receptor-deficient mice intratracheally with LPS and examined the expression of KC. LPS-treated, TNF receptor-deficient mice showed much less KC mRNA in airway epithelial cells compared with wild-type mice. In contrast, a similar number of KC-expressing cells was seen in the lung periphery. Thus, upregulation of KC by Clara cells in the setting of LPS stimulation is largely dependent on TNF-alpha originating from alveolar macrophages. These findings shed light on macrophage-Clara cell interactions in regulating the pulmonary inflammatory response to LPS.
Am J Respir Cell Mol Biol 2008 Jan
PMID:Tumor necrosis factor-alpha from macrophages enhances LPS-induced clara cell expression of keratinocyte-derived chemokine. 1767 86

Cytokine and chemokine receptors play a key role in inflammation caused by rheumatoid arthritis (RA). Two isoforms of human CC chemokine receptor R2 (CCR2), the receptor of monocyte chemoattractant protein 1 (MCP-1), have been identified but their relative expression in fibroblast-like synoviocytes (FLS) and their contribution to inflammatory responses mediated by MCP-1 or inflammatory cytokines in patients with RA remain uncertain. We examined the pattern of expression of two CCR2 isoforms upon stimulation by proinflammatory cytokines and CD40 ligation. FLS were prepared from the synovial tissues of RA patients and cultured in the presence of MCP-1, soluble CD40 ligand (sCD40L), TGF-beta, IL-1beta, IL-18, IL-15, and LPS. CCR2A and CCR2B expression was examined by immunohistochemistry, RT-PCR and western blot analysis. IL-15, TNF-alpha and MCP-1 production was determined by ELISA. Immunohistochemistry showed that CCR2A is highly expressed in RA synovium compared with OA synovium. Transcripts of both CCR2A and CCR2B were detected in FLS. Exogenous MCP-1, CD40L, TGF-beta, and IL-15 significantly increased the expression of CCR2A but not CCR2B. Exposure of FLS to sCD40L caused strong upregulation of CCR2A but not of CCR2B protein expression. MCP-1 increased the proliferation of FLS and the production of IL-15, TNF-alpha, and IL-18. Because CCR2A is the main target of regulation by cytokines and CD40 ligation, the relatively higher expression of CCR2A on the cell surface suggests that this isoform of MCP-1 receptor functions as the principal mediator of inflammatory signals in RA FLS.
Exp Mol Med 2007 Aug 31
PMID:Expression of CCR2A, an isoform of MCP-1 receptor, is increased by MCP-1, CD40 ligand and TGF-beta in fibroblast like synoviocytes of patients with RA. 1793 38

We have proposed that luteal cells undergo apoptosis-dependent phagocytosis by invading monocyte-derived macrophages in regressive corpora lutea of the rat. Accumulation of monocytes/macrophages seems to be mediated by monocyte chemoattractant protein 1 (MCP-1) or CCL2, because apoptosis and the production of MCP-1 mRNA occur simultaneously, but in different luteal cells, in a manner dependent on nuclear factor kappaB (NF-kappaB). In this study, we determined the mechanisms underlying the induction of these two events using primary cultures of rat luteal cells. We found that the activity of the transcription factor activator protein 1 (AP-1) increased during culturing concomitantly with an increase of MCP-1 mRNA. The increase of MCP-1 mRNA was abolished when cultures were maintained in the presence of an inhibitor of either AP-1 or c-Jun amino-terminal kinase (JNK) that phosphorylates and activates c-Jun, a subunit of AP-1. Furthermore, the presence of an inhibitor of NF-kappaB abrogated an increase in the activity of both AP-1 and JNK. In contrast, the induction of apoptosis in cultured luteal cells required the action of JNK but appeared to be independent of AP-1. This may explain why apoptosis and MCP-1 mRNA production are concomitantly but differentially induced in distinct luteal cells. We therefore suggest the following signaling pathways for the induction of apoptosis and mcp-1 gene expression during involution of the corpus luteum; NF-kappaB's actions lead to the activation of JNK, and the active JNK, at one side, stimulates mcp-1 gene transcription by activating AP-1 and, at the other side, induces apoptosis.
Mol Reprod Dev 2008 Jun
PMID:Activator protein 1-mediated expression of monocyte chemoattractant protein 1 in cultured rat luteal cells. 1815 68

Tumor necrosis factor (TNF)-alpha is central to the endometriotic disease process. TNF-alpha receptor signaling regulates epithelial cell secretion of inflammation and invasion mediators. Because epithelial cells are a disease-inducing component of the endometriotic lesion, we explored the response of 12Z immortalized human epithelial endometriotic cells to TNF-alpha. This report reveals the impact of disruption of established TNF-alpha-induced signaling cascades on the expression of biomarkers of inflammation and epithelial-mesenchymal transition (EMT) from endometriotic epithelial cells. Note that we show the molecular potential of soluble TNF-R1 [TNF binding protein (TBP)] and a panel of small molecule kinase inhibitors to block endometriotic gene expression directly. The TNF-alpha receptor is demonstrated to signal through IkappaB kinase complex (IKK) 2 > IkappaB > nuclear factor kappaB, extracellular signal-regulated kinase > mitogen-activated protein kinase kinase (MEK), p38, and phosphatidylinositol 3-kinase (PI3K) > Akt1/2. TNF-alpha induces the expression of transcripts for inflammatory mediators interleukin (IL)-6, IL-8, regulated on activation normal T cell expressed and secreted, TNF-alpha, granulocyte macrophage-colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein (MCP)-1 and also invasion mediators matrix metalloproteinase (MMP)-7, MMP-9, and intracellular adhesion molecule-1. Indeed, TBP inhibits the TNF-alpha-induced expression of all the above endometriotic genes in 12Z endometriotic epithelial cells. The secretion of IL-6, IL-8, GMCSF, and MCP-1 by TNF-alpha is blocked by TBP. Interestingly, MEK, p38, and IKK inhibitors block TNF-alpha-induced IL-8, IL-6, and GM-CSF secretion and 12z invasion, whereas the PI3K inhibitors do not. The only inhibitor to block MCP-1 expression is the p38 inhibitor. Last, TBP, MEK inhibitor, or p38 inhibitor also block cell surface expression of N-cadherin, a marker of mesenchymal cells. Taken together, these results demonstrate that interruption of TNF-alpha-induced signaling pathways in human endometriotic epithelial cells results in decreased expression and secretion of biomarkers for inflammation, EMT, and disease progression.
Mol Pharmacol 2008 May
PMID:Tumor necrosis factor-alpha regulates inflammatory and mesenchymal responses via mitogen-activated protein kinase kinase, p38, and nuclear factor kappaB in human endometriotic epithelial cells. 1825 6

Ischemia and reperfusion injury (IRI) contributes to the development of chronic interstitial fibrosis/tubular atrophy in renal allograft patients. Cyclooxygenase (COX) 1 and 2 actively participate in acute ischemic injury by activating endothelial cells and inducing oxidative stress. Furthermore, blockade of COX 1 and 2 has been associated with organ improvement after ischemic damage. The aim of this study was to evaluate the role of COX 1 and 2 in the development of fibrosis by performing a COX 1 and 2 blockade immediately before IRI. We subjected C57Bl/6 male mice to 60 min of unilateral renal pedicle occlusion. Prior to surgery mice were either treated with indomethacin (IMT) at days -1 and 0 or were untreated. Blood and kidney samples were collected 6 wks after IRI. Kidney samples were analyzed by real-time reverse transcription-polymerase chain reaction for expression of transforming growth factor beta (TGF-beta), monocyte chemoattractant protein 1 (MCP-1), osteopontin (OPN), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1 beta, IL-10, heme oxygenase 1 (HO-1), vimentin, connective-tissue growth factor (CTGF), collagen I, and bone morphogenic protein 7 (BMP-7). To assess tissue fibrosis we performed morphometric analyses and Sirius red staining. We also performed immunohistochemical analysis of anti-actin smooth muscle. Renal function did not significantly differ between groups. Animals pretreated with IMT showed significantly less interstitial fibrosis than nontreated animals. Gene transcript analyses showed decreased expression of TGF-beta, MCP-1, TNF-alpha, IL-1-beta, vimentin, collagen I, CTGF, and IL-10 mRNA (all P < 0.05). Moreover, HO-1 mRNA was increased in animals pretreated with IMT (P < 0.05). Conversely, IMT treatment decreased osteopontin expression and enhanced BMP-7 expression, although these levels did not reach statistical significance when compared with control expression levels. The blockade of COX 1 and 2 resulted in less tissue fibrosis, which was associated with a decrease in proinflammatory cytokines and enhancement of the protective cellular response.
Mol Med
PMID:Inhibition of COX 1 and 2 prior to renal ischemia/reperfusion injury decreases the development of fibrosis. 1876 37


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