Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the kinetics of parasite replication, leukocyte migration, and cytokine/chemokine mRNA expression in the heart tissue from animals infected with the Colombiana strain of Trypanosoma cruzi. Cardiac tissue parasitism was noticeable at 15 days, peaked around 30 days and was dramatically reduced at 120 days postinfection (p.i.). Kinetic studies showed that the inflammatory infiltrate was dominated by the presence of alphabetaT CD3(+ )CD4(+ )CD8(-), alphabetaT CD3(+ )CD4(-)CD8(+ )lymphocytes and macrophages. The mRNA expression of the monokines IL-1beta and IL-12(p40) was elevated at 15 days p.i. and controlled at later time points. In contrast, TNF-alpha mRNA was expressed throughout the infection. Interestingly, we found that at 15 and 30 days p.i. cytokine expression was dominated by the presence of IFN-gamma mRNA, whereas at 60 days or later time points the balance of type 1 and type 2 cytokines was switched in favor of IL-4 and IL-10 mRNAs. The chemokine mRNAs encoding JE, MIP-1alpha, MIP-1beta, KC, and MIP-2 were all mainly expressed at 15 and/or 30 days p.i. and diminished thereafter. In contrast, the expression of RANTES, MIG and IP-10 mRNAs was augmented at 15 days p.i. and persisted at high levels up to 120 days p.i. Taken together, our results indicate that regulation of IFN-gamma and chemokine expression, associated with decreased tissue parasitism, may be largely responsible for the control of inflammation and immunopathology observed in the cardiac tissue of animals infected with T. cruzi.
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PMID:Kinetics of cytokine gene expression in experimental chagasic cardiomyopathy: tissue parasitism and endogenous IFN-gamma as important determinants of chemokine mRNA expression during infection with Trypanosoma cruzi. 1096 68

Chemokines play an essential role in immune and inflammatory reactions via the recruitment of leukocytes. Studying the role of chemokines in vivo is complicated by the redundancy of their action and by their promiscuous receptor usage. The simultaneous analysis of several chemokines is, therefore, advantageous in order to obtain a comprehensive view of chemokine participation in inflammatory and infectious processes. At present, no multi-probe detection systems are available for the analysis of recently described chemokines. In this study, new multi-probe RNase protection assay (RPA) template sets were developed for the analysis of murine chemokines. Chemokine cDNA fragments were generated by RT-PCR and individually subcloned into the plasmid pGEM-T providing a T7 promotor. In this way, two multi-probe template sets were constructed each containing six chemokine sequences (CXCL12/SDF-1, XCL1/lymphotactin, CCL20/exodus-1, CCL25/TECK, CX3CL1/fractalkine, CXCL1/KC, and CCL20/MDC, CXCL9/MIG, CCL9/10/MIP-1gamma, CXCL13/BLC, CCL12/MCP-5, CCL19/ELC, respectively) and templates for the two house-keeping genes L32 and GAPDH. The evaluation of these RPA template sets in various murine models demonstrated their suitability for the analysis of the above chemokines both under constitutive and infection-induced conditions. To reduce the personal radiation hazard, we found that 32P could be replaced by 33P without any loss of assay-sensitivity. These new RPA multi-probe sets provide valuable tools for the simultaneous quantitative determination of gene expression of multiple murine chemokines of both constitutive and inducible type.
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PMID:Novel multi-probe RNase protection assay (RPA) sets for the detection of murine chemokine gene expression. 1122 73

Macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19 are members of the CC chemokine subfamily which exert their effects through specific receptors, CCR6 and CCR7, respectively. Previously, we have reported that human neutrophils have the capacity to produce a number of chemokines, including IL-8/CXCL8, GROalpha/CXCL1, IP-10/CXCL10, and MIG/CXCL9. Herein, we show that neutrophils also have the ability to express and release MIP-3alpha/CCL20 and MIP-3beta/CCL19 when cultured with either LPS or TNF-alpha. We also report that MIP-3alpha/CCL20 and MIP-3beta/CCL19 production by LPS-stimulated neutrophils is negatively modulated by IL-10. Remarkably, we found that supernatants harvested from stimulated neutrophils not only induced chemotaxis of both immature and mature dendritic cells (DC), but also triggered rapid integrin-dependent adhesion of CCR6- and CCR7-expressing lymphocytes to purified VCAM-1 and ICAM-1, respectively. Importantly, both chemotaxis and rapid integrin-dependent adhesion were dramatically suppressed by anti-MIP-3alpha/CCL20 and anti-MIP-3beta/CCL19 neutralizing antibodies, indicating that MIP-3alpha/CCL20 and MIP-3beta/CCL19 present in the supernatants were both biologically active. As these chemokines are primarily chemotactic for DC and specific lymphocyte subsets, the ability of neutrophils to produce MIP-3alpha/CCL20 and MIP-3beta/CCL19 might be significant in orchestrating the recruitment of these cell types to the inflamed sites and therefore in contributing to the regulation of the immune response.
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PMID:Neutrophils produce biologically active macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19. 1144 50

We used quantitative PCR to investigate the expression of chemokines and chemokine receptors in two Th1-mediated murine models of inflammatory bowel disease (IBD). First, mRNA levels encoding the chemokines MIG, RANTES, lymphotactin, MIP-3alpha, TCA-3, TARC, MIP-3beta, LIX, MCP-1 and MIP-1beta and the receptors CCR4, CCR6 and CCR2 were significantly increased in chronically inflamed colons of IL-10-/- mice when compared with wildtype mice. Interestingly, reversal of colitis in IL-10-/- mice by anti-IL-12 mAb was accompanied by the inhibition in the expression of LIX, lymphotactin, MCP-1, MIG, MIP-3alpha, MIP-3beta, TCA-3, CCR2 and CCR4, whereas the increased mRNA levels of MIP-1beta, RANTES, TARC and CCR6 were unaffected. Second, to investigate which chemokines and receptors were up-regulated during the inductive phase of colitis, we employed the CD4+CD45RBhigh T cell transfer model. At 4 and 8 weeks after reconstitution of Rag-2-/- mice the mRNA levels of IP-10, MCP-1, MDC, MIG, TARC, RANTES, CCR4 and CCR5 were significantly increased prior to the appearance of macroscopic lesions. Other chemokines and chemokine receptors were clearly associated with the acute phase of the disease when lesions were evident. The sum of our studies with these two models identifies chemokines that are expressed at constant levels, irrespective of inflammatory responses, and those that are specifically associated with acute and/or chronic stages of Th1-driven colitis.
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PMID:Characterization of chemokines and chemokine receptors in two murine models of inflammatory bowel disease: IL-10-/- mice and Rag-2-/- mice reconstituted with CD4+CD45RBhigh T cells. 1146 3

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

Cytokine and chemokine responses during anamnestic type-1 and type-2 lung granuloma formation were evaluated in mice at 6,12,18 and 24-months of age. Lesions were induced by embolizing Sepharose beads coupled to Mycobacterium bovis purified protein derivative or soluble Schistosoma mansoni egg antigens. Type-1 inflammation was reduced by 18 months, whereas type-2 granulomas not until 24 months of age. In type-1 draining lymph nodes cultures, interferon-gamma (IFNgamma) declined to a nadir by 18, and then partly recovered at 24 months. In contrast, IL-4 was not significantly impaired in type-2 cultures until 24 months. Type-1 and 2 node cultures also displayed decreased IL-13, but paradoxically enhanced IL-5 production at 24 months. Chemokine transcripts in granulomatous lungs displayed age-related alterations. In the type-1 response, CXCL9 (monokine-induced by IFNgamma) declined with age then partly recovered at 24 months parallelling lymph node IFNgamma levels. Transcripts for MIP-2/CXCL2, IP-10/CXCL10, MCP-1/CCL2, and MCP-5/CCL12 increased at 24 months. In the type-2 response MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12 and TARC/CCL17 collapsed at 24 months paralleling local IL-4 transcript levels, yet some chemokine transcripts such as KC/CXCL1 and eotaxin/CCL11 were unaffected. These findings suggest that cytokine and chemokine responses degrade differentially with age shifting Th1/Th2 crossregulatory pressures and local expression of chemokines.
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PMID:Differential effects of ageing on cytokine and chemokine responses during type-1 (mycobacterial) and type-2 (schistosomal) pulmonary granulomatous inflammation in mice. 1174 43

Using cDNA microarray technology, the expression of chemokine genes in the elicitation site of 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity (CHS) was examined in mice. Of the 33 genes analyzed, levels of 11 gene expressions changed, and these can be assigned to four groups based on their kinetic patterns; (1) LARC/CCL20 whose mRNA level increased rapidly at 3 h post-challenge and then gradually decreased, (2) JE/CCL2, MARC/CCL7, MIP-1gamma/CCL9, monocyte chemoattractant protein (MCP)-5/CCL12, ELC/CCL19 and BRAK/CXCL14 whose mRNA levels increased with time and reached the maximum at 6-9 h post-challenge, (3) LIX/CXCL5, Mig/CXCL9 and IP-10/CXCL10 whose mRNA levels increased gradually at least up to 12 h post challenge, and (4) SLC/CCL21 whose mRNA level decreased gradually with time after challenge. The findings suggest that sequential expression of chemokine genes is essential for orientating non-specific skin response to hapten-specific CHS response through the recruitment of inflammatory cells such as neutrophils, monocytes/macrophages and T-cells from the circulation into the tissue site.
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PMID:Kinetic profiles of sequential gene expressions for chemokines in mice with contact hypersensitivity. 1264 22

The levels of monocyte intracellular monokines (TNFalpha, MIP, and MIG) in patients with cancer or bacterial infection were studied by multiparameter flow cytometry and comparative fluorescence analysis. TNFalpha, MIP, and MIG levels in peripheral blood of patients with cancer or bacterial infection were higher than in normal controls (p < 0.005). In normal controls, no significant relationships were found among TNFalpha, MIG, MIP levels, monocyte count, and lymphocyte count in peripheral blood. In cancer patients, TNFalpha was strongly related to MIP (r = 0.809, p < 0.001) and MIG (r = 0.773, p < 0.001). Of the 3 monokines, TNFalpha and MIG levels were related to monocyte count, but none showed correlation with lymphocyte count in cancer patients. In patients with bacterial infection, TNFalpha was not significantly related to MIP (r = 0.423, p = 0.051), but it was related to MIG (r = 0.457; p = 0.033). None of the monokines (TNFalpha, MIP, MIG) was related to the monocyte count, but the MIP level was related to the peripheral blood lymphocyte count in patients with bacterial infection (r = 0.559, p = 0.008). These results suggest that circulating monocytes may play an important role in both cancer and bacterial infection through increased production of monokines. Moreover, correlations of the monokine levels with each other and their relationships to the monocyte count differ in patients with cancer and bacterial infection.
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PMID:Monokine levels in cancer and infection. 1281 18

Macrophages have a central role in innate-immune responses to bacteria. In the present work, we show that infection of human macrophages with Gram-positive pathogenic Streptococcus pyogenes or nonpathogenic Lactobacillus rhamnosus GG enhances mRNA expression of inflammatory chemokine ligands CCL2/monocyte chemoattractant protein-1 (MCP-1), CCL3/macrophage-inflammatory protein-1alpha (MIP-1alpha), CCL5/regulated on activation, normal T expressed and secreted, CCL7/MCP-3, CCL19/MIP-3beta, and CCL20/MIP-3alpha and CXC chemokine ligands CXCL8/interleukin (IL)-8, CXCL9/monokine induced by interferon-gamma (IFN-gamma), and CXCL10/IFN-inducible protein 10. Bacteria-induced CCL2, CCL7, CXCL9, and CXCL10 mRNA expression was partially dependent on ongoing protein synthesis. The expression of these chemokines and of CCL19 was dependent on bacteria-induced IFN-alpha/beta production. CCL19 and CCL20 mRNA expression was up-regulated by IL-1beta or tumor necrosis factor alpha (TNF-alpha), and in addition, IFN-alpha together with TNF-alpha further enhanced CCL19 gene expression. Synergy between IFN-alpha and TNF-alpha was also seen for CXCL9 and CXCL10 mRNA expression. Bacteria-stimulated macrophage supernatants induced the migration of T helper cell type 1 (Th1) cells, suggesting that in human macrophages, these bacteria can stimulate efficient inflammatory chemokine gene expression including those that recruit Th1 cells to the site of inflammation. Furthermore, L. rhamnosus-induced Th1 chemokine production could in part explain the proposed antiallergenic properties of this bacterium.
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PMID:Lactobacilli and streptococci induce inflammatory chemokine production in human macrophages that stimulates Th1 cell chemotaxis. 1294 43

We have characterized leukocyte migration to the pleural cavity in a methylated-BSA (mBSA)-induced model of murine delayed-type hypersensitivity and evaluated the ability of IL-4 and IL-10 to modulate this response. Neutrophils, macrophages, T cells, and dendritic cells migrated to the pleural cavity in a time-dependent fashion following direct intrapleural antigen challenge, with neutrophils comprising the majority of exudate leukocytes in the cavity within the first 24 h and the number of mononuclear cells increasing at later times. Real-time quantitative PCR analysis of infiltrating leukocytes revealed a marked elevation of steady-state mRNA levels of IL-1beta and TNFalpha and the chemokines KC, MIP-2, CXCL9, CXCL10, CXCL11, CCL2, CCL3, and CCL4 at 6 h postchallenge, which diminished over time. In contrast, gammaIFN mRNA levels were maximal at 24 h and CCL5 expression was sustained throughout 72 h. ELISA analysis of pleural exudate fluid revealed significant elevations of KC and CCL2 protein levels at 6 h postantigen challenge and a peak increase in gammaIFN protein at 24 h, confirming our mRNA observations. Administration of recombinant murine IL-4 or IL-10 prior to challenge significantly blocked cell trafficking to the pleural cavity as well as peak levels of exudate gammaIFN, with IL-4 being more potent in impairing these responses. IL-4 administration also increased the proportion of naive T cells in the pleural cavity, as judged by CD62L and CD45RB expression. These results indicate that this in vivo model demonstrates a pattern of events associated with Th1-mediated leukocyte trafficking and underscore the potential utility of this in vivo model for evaluating therapeutic inhibitors of leukocyte trafficking.
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PMID:Impairment of leukocyte trafficking in a murine pleuritis model by IL-4 and IL-10. 1452 70


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