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 are a group of cytokines that are responsible for the influx of blood cells, including T and B lymphocytes, monocytes, neutrophils, eosinophils and basophils, in allergic and other inflammatory conditions. They function as G protein-coupled chemotactic factors which also activate the cells with which they interact. Certain chemokines function within the afferent arm of the immune system, in which antigen is processed and antibody formation initiated, and others are active within the effector pathways of cellular immunity and late-phase allergic reactions. Th2 lymphocytes, which are critical for allergy, employ the CC chemokine receptors CCR4 and CCR8 with the ligands thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and I-309, respectively. The chemokine receptor CCR3 and ligands monocyte chemoattractant protein (MCP)-3, MCP-4, regulated upon activation normal T cell expressed and secreted (RANTES) and eotaxins I and II are of particular relevance for the recruitment and activation of eosinophils. Th1 reactions depend upon interferon gamma-induced CXC chemokines interferon- inducible protein (IP)-10, interferon-inducible T cell-alpha chemoattractant (iTAC) and monokine induced by interferon-gamma (MiG), which bind to chemokine receptor CXCR3.
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PMID:Chemokines, chemokine receptors and allergy. 1134 Mar 25

Host-derived chemoattractant factors are suggested to play crucial roles in leukocyte recruitment elicited by inflammatory stimuli in vitro and in vivo. However, in the case of acute bacterial infections, pathogen-derived chemoattractant factors are also present, and it has not yet been clarified how cross-talk between chemoattractant receptors orchestrates diapedesis of leukocytes in this context of complex chemoattractant arrays. To investigate the role of chemokine (host-derived) and formyl peptide (pathogen-derived) chemoattractants in leukocyte extravasation in life-threatening infectious diseases, we used a mouse model of pneumococcal pneumonia. We found an increase in mRNA expression of eight chemokines (RANTES, macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-2, IP-10, monocyte chemoattractant protein (MCP)-1, T cell activation 3, and KC) within the lungs during the course of infection. KC and MIP-2 protein expression closely preceded pulmonary neutrophil recruitment, whereas MCP-1 protein production coincided more closely than MIP-1alpha with the kinetics of macrophage infiltration. In situ hybridization of MCP-1 mRNA suggested that MCP-1 expression started at peribronchovascular regions and expanded to alveoli-facing epithelial cells and infiltrated macrophages. Interestingly, administration of a neutralizing Ab against MCP-1, RANTES, or MIP-1alpha alone did not prevent macrophage infiltration into infected alveoli, whereas combination of the three Abs significantly reduced macrophage infiltration without affecting neutrophil recruitment. The use of an antagonist to N-formyl peptides, N-t-Boc-Phe-D-Leu-Phe-D-Leu-Phe, reduced both macrophages and neutrophils significantly. These data demonstrate that a complex chemokine network is activated in response to pulmonary pneumococcal infection, and also suggest an important role for fMLP receptor in monocyte/macrophage recruitment in that model.
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PMID:Role of chemokines and formyl peptides in pneumococcal pneumonia-induced monocyte/macrophage recruitment. 1139 Apr 86

Recent evidence suggests that T-lymphocyte extravasation and CNS-parenchymal infiltration during autoimmune disease might be regulated by antigen-presenting (ED2(+)) cerebral/spinal perivascular phagocytes (CPP/SPP). Since the massive erythrocytic and leukocytic infiltrates in the CNS of rats with experimental allergic encephalomyelitis do not allow a precise differentiation between CPP/SPP and the invading cells in the Virchow-Robin space, we developed a new immune-response model whereby the extravasation of T-lymphocytes was not followed by other blood cells. Adult Lewis rats were sensitized to horseradish peroxidase (HRP). Subsequent intracerebroventricular (i.c.v.) injections of HRP and/or Fluoro-Emerald (FE) served to: (1) challenge the primed T-lymphocytes and (2) label the CPP/SPP for additional immunocytochemical analysis. We found that 24 h and 3 days after single, double, or triple antigen boosting T-lymphocytes (R73(+), W3/25(+), OX50(+)) entered the Virchow-Robin space but did not break through the astrocytic glia limitans. Instead they adhered to HRP-containing activated CPP/SPP (mabs OX-6(+), SILK6(+), CD40(+), CD80(+), CD86(+)). This selective contact was mediated neither by cell adhesion molecules (P-selectin, ICAM-1, VCAM-1), nor promoted by chemokine receptors (CCR1, CCR5) or chemokines (monocyte chemoattractant protein (MCP)-1, MIP-1alpha, MIP-1beta, RANTES). This non-inflammatory, but antigen-dependent lymphocyte extravasation provides optimal conditions to further study the CNS immune response.
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PMID:Exogenous antigen containing perivascular phagocytes induce a non-encephalitogenic extravasation of primed lymphocytes. 1143 Oct 2

Inflammatory chemokines recruit various populations of immune cells that initiate and maintain the inflammatory response against foreign Ags. Although such a response is necessary for the elimination of the Ag, the inflammation has to be eventually resolved in a healthy organism. Neuropeptides such as vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), released after antigenic stimulation, contribute to the termination of an inflammatory response primarily by inhibiting the production of proinflammatory cytokines. Here we investigated the effects of VIP and PACAP on chemokine production. We report that VIP and PACAP inhibit the expression of the macrophage-derived CXC chemokines macrophage inflammatory protein-2 and KC (IL-8), and of the CC chemokines MIP-1alpha, MIP-1beta, monocyte chemoattractant protein 1, and RANTES in vivo and in vitro. The inhibition of chemokine gene expression correlates with an inhibitory effect of VIP/PACAP on NF-kappaB binding and transactivating activity. The VIP/PACAP inhibition of both chemokine production and of NF-kappaB binding and transactivating activity is mediated through the specific VIP receptor VPAC1, and involves both cAMP-dependent and -independent intracellular pathways. In an in vivo model of acute peritonitis, the inhibition of chemokine production by VIP/PACAP leads to a significant reduction in the recruitment of polymorphonuclear cells, macrophages, and lymphocytes into the peritoneal cavity. These findings support the proposed role of VIP and PACAP as key endogenous anti-inflammatory agents and describe a novel mechanism, i.e., the inhibition of the production of macrophage-derived chemokines.
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PMID:Inhibition of endotoxin-induced macrophage chemokine production by vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide in vitro and in vivo. 1144 Nov 5

To explore the roles of chemokines in type 1 and type 2 responses in vivo, we examined mRNA expression for a panel of up to 17 chemokines in experimental mouse models using Schistosoma mansoni. These studies revealed that Mig (monokine induced by gamma interferon), cytokine-responsive gene 2/10-kDa interferon-inducible protein, RANTES, lymphotactin, macrophage inflammatory protein 1beta (MIP-1beta), JE/monocyte chemoattractant protein 1, and MIP-2 are associated with type 1 egg-induced responses and that thymus-derived chemotactic agent 3 (TCA3), eotaxin, MIP-1alpha, and MIP-1gamma are associated with type 2 egg-induced responses. After cercarial infection, both type 1-associated and type 2-associated chemokines were elevated in the livers of infected mice presensitized with eggs and recombinant interleukin-12 (rIL-12), a regimen that diminishes pathology. Neutralization of IL-12 or gamma interferon during egg deposition reversed the effects of prior treatment with rIL-12, leading to a return to larger granulomas; persistently elevated expression of TCA3, eotaxin, and MIP-1alpha; and a marked reduction in the expression of type 1-associated chemokines despite the maintenance of a dominant type 1 cytokine response in the draining lymph nodes. Our findings suggest that there are patterns of coordinate chemokine expression characteristic of type 1 and type 2 responses in vivo; that the cells recruited by a given pattern of chemokines may differ, depending on the composition of peripheral populations; and that patterns of tissue expression of chemokines may determine the character of an inflammatory response independently of the dominant pattern of differentiation of antigen-specific T cells. Our data reveal new relationships between chemokines and polarized immune responses and suggest that end organ inflammation might be altered by chemokine blockade without necessitating reversal of the phenotype of the majority of differentiated T cells.
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PMID:Patterns of chemokine expression in models of Schistosoma mansoni inflammation and infection reveal relationships between type 1 and type 2 responses and chemokines in vivo. 1159 48

1. Chemokine expression and function was monitored in an experimental model of granulomatous tissue formation after injection of croton oil in complete Freund's adjuvant (CO/CFA) into mouse dorsal air-pouches up to 28 days. 2. In the first week, mast cell degranulation and leukocyte influx (mononuclear cell, MNC, and polymorphonuclear cell, PMN) were associated with CXCR2, KC and macrophage inflammatory protein (MIP)-2 mRNA expression, as determined by TaqMan reverse transcriptase-polymerase chain reaction. KC ( approximately 400 pg x mg protein(-1), n=12) and MIP-2 (approximately 800 pg x mg protein(-1), n=12) proteins peaked at day 7, together with myeloperoxidase (MPO) activity. Highest MIP-1alpha (>1 ng x mg protein(-1), n=12) levels were measured at day 3. 3. After day 7, a gradual increase in CCR2 and CCR5 mRNA, monocyte chemoattractant protein (MCP)-1 mRNA and protein expression was measured. MCP-1 protein peaked at day 21 (approximately 150 pg x mg protein(-1), n=12) and was predominantly expressed by mast cells. A gradual increase in N-acetyl-beta-D-glucosaminidase (NAG) activity (maximal at 28 days) was also measured. 4. An antiserum against MIP-1alpha did not modify the inflammatory response measured at day 7 (except for a 50% reduction in MIP-1alpha levels), but provoked a significant increase in MPO, NAG and MCP-1 levels as measured at day 21 (n=6, P<0.05). An antiserum to MCP-1 reduced NAG activity at day 21 but increased MPO activity values (n=8, P<0.05). 5. In conclusion, we have shown that CO/CFA initiates a complex inflammatory reaction in which initial expression of MIP-1alpha serves a protective role whereas delayed expression of MCP-1 seems to have a genuine pro-inflammatory role.
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PMID:Analysis of the temporal expression of chemokines and chemokine receptors during experimental granulomatous inflammation: role and expression of MIP-1alpha and MCP-1. 1170 36

Previous studies have documented that the ability to heal wounds declines with age. Although many factors contribute to this age-associated deficit, one variable that has not been carefully examined is leukocyte recruitment and function in wounds. This investigation compares the inflammatory response in excisional wounds of young (age 8 wk) and aged (age 22 mo) mice. In the early inflammatory response, neutrophil content of wounds was similar for both aged and young mice. In contrast, macrophage levels were 56% higher in aged versus young mice (81 +/- 20 vs 52 +/- 13 cells per mm2). In the later inflammatory response, wounds of aged mice exhibited a delay in T cell infiltration, with maximum T cell levels at day 10 in aged mice versus day 7 in young mice. Despite this delay, the eventual peak concentration of T cells was 23% higher in the wounds of aged mice (152 +/- 11 cells per mm2 vs 124 +/- 21cells per mm2). The observed alterations in inflammatory cell content suggested that chemokine production might be altered with age. An elevation of monocyte chemoattractant protein (MCP-1) levels was observed in wounds of aged mice. RNase protection studies, however, revealed that the production of most chemokines, including MIP-2, MIP-1alpha, MIP-1beta, and eotaxin, tended to decline with age. Because optimal wound healing requires both appropriate macrophage infiltration and phagocytic activity, phagocytosis was examined. Compared to young mice, wound macrophages from aged mice exhibited a 37%-43% reduction in phagocytic capacity. Taken together, the data demonstrate age-related shifts in both macrophage and T cell infiltration into wounds, alterations in chemokine content, and a concurrent decline in wound macrophage phagocytic function. These alterations may contribute to the delayed repair response of aging.
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PMID:Age-related alterations in the inflammatory response to dermal injury. 1171 Sep 9

The intracerebral formation of inflammatory infiltrates is a complex process, which may be regulated by chemokines. This study defines the kinetics and cellular sources of T cell- and macrophage-attracting chemokines in murine Toxoplasma encephalitis (TE) by ribonuclease protection assay, reverse transcription-PCR, in situ hybridization, and immunohistochemistry. Whereas astrocytes were the major source of interferon (IFN)-gamma-inducible protein-10 (CRG-2/IP-10) and monocyte chemoattractant protein (MCP)-1, microglia expressed RANTES, monokine induced by IFN-gamma (MuMIG) and occasionally CRG-2/IP-10 RNA. Despite being ubiquitously activated, only astrocytes and microglia confined to inflammatory infiltrates expressed chemokine genes. Intracerebral leukocytes transcribed RANTES, MuMIG, and occasionally CRG-2/IP-10 and MCP-1. IFN-gamma-deficient mice failed to produce CRG-2/IP-10, MuMIG, RANTES and expressed macrophage inflammatory protein (MIP-1)alpha, MIP-1 beta, and MCP-1 mRNA at reduced levels, functionally resulting in a strongly reduced recruitment of leukocytes across the blood-brain barrier and prevented their further invasion of the brain parenchyma. Since T cells are the single source of IFN-gamma in TE, these findings indicate that T cells pave the way of leukocytes to parenchymatous parasites via IFN-gamma.
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PMID:Chemokines are differentially expressed by astrocytes, microglia and inflammatory leukocytes in Toxoplasma encephalitis and critically regulated by interferon-gamma. 1193 61

Chemokines direct the recruitment of leukocytes to inflammatory sites and may also participate in the regulation of cytokine production by naive T helper cells. Chemokine production by blood monocytes was investigated by intracytoplasmic staining in interferon-beta (IFN-beta)-treated multiple sclerosis (MS) patients, untreated MS patients, and healthy controls. Under unstimulated conditions, no differences in the production of interleukin-8 (IL-8), IFN-inducible protein 10 (IP-10), monokine induced by interferon-gamma (Mig), monocyte chemoattractant protein-1 (MCP-1), and monocyte chemoattractant protein-3 (MCP-3) were seen between untreated MS patients and controls. Chemokine production by monocytes following T cell activation was decreased in MS patients taking IFN-beta compared to controls and untreated MS patients. Unlike other chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha) production by monocytes was significantly decreased in untreated MS patients compared to controls, and IFN-beta treatment increased MIP-1alpha expression to the level seen in controls. In vitro addition of IFN-beta1b to peripheral blood mononuclear cells (PBMC) cultures tended to decrease the production of IL-8, IP-10, Mig, MCP-1, and MCP-3, but not of MIP-1alpha. These findings suggest that IFN-beta treatment may have a differential affect on chemokine production by monocytes. Longitudinal studies must be done to confirm these observations.
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PMID:Interferon-beta treatment alters peripheral blood monocytes chemokine production in MS patients. 1202 Sep 72

Immunohistochemical studies on the time-dependent expression of the chemokines such as interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha were performed on 50 human skin wounds with different wound ages (group I 0-12 h, group II 1-4 days, group III 7-14 days and group IV 17-21 days). In the wound specimens with wound ages between 4 and 12 h, neutrophils mainly showed positive reactions for IL-8, MCP-1 and MIP-1alpha. With increasing wound ages, macrophages and fibroblasts were positively stained with anti-IL-8, MIP-1alpha and MCP-1 antibodies. Morphometrically, there was a similar distribution in the positive ratios of the inflammatory cells among IL-8, MCP-1 and MIP-alpha. The positive ratios of each chemokine were very low in group I and a considerable increase of the positive ratios in each chemokine was observed in group II (mean +/- standard error IL-8: 59.8 +/- 2.1%, MCP-1: 42.4 +/- 3.1% and MIP-1alpha: 50.4 +/- 3.7%). Although the positive ratios for each chemokine gradually decreased according to the wound age, the mean positive ratios in groups III and IV were significantly higher than those in group I. From the forensic aspect, these chemokines are considered useful markers for wound age determination. Thus, ratios of > 50% for IL-8, > 30% for MCP-1 or > 40% for MIP-1alpha indicate a wound age of at least I day. Moreover, the combined investigation of these three chemokines can make wound age determination more objective and accurate.
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PMID:Immunohistochemical detection of chemokines in human skin wounds and its application to wound age determination. 1205 26


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