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)

The CC chemokine receptor (CCR) 8 belongs to the seven transmembrane-spanning receptor family and functionally responds to the eukaryotic CC chemokines I-309, thymus and activation-regulated chemokine, macrophage inflammatory protein-1 beta (MIP-1b) and to the products viral MIP-I and viral MIP-II of the Kaposi-associated herpesvirus (HHV-8). Although it has not yet been fully characterised, its restricted expression to lymphoid tissues, i.e. thymus, spleen and lymph nodes, and its abundant up-regulation in Th2 lymphocytes suggest a potential role in lymphocyte activation, migration and differentiation and in allergic diseases. In this article we review the data known up to now related to CCR8 from cloning to protein structure, expression patterns and functional activation by its agonists.
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PMID:Structure and function of the CC chemokine receptor (CCR) 8. 1061 8

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

The Paramyxovirus respiratory syncytial virus (RSV) is the primary etiologic agent of serious epidemic lower respiratory tract disease in infants, immunosuppressed patients, and the elderly. Lower tract infection with RSV is characterized by a pronounced peribronchial mononuclear infiltrate, with eosinophilic and basophilic degranulation. Because RSV replication is restricted to airway epithelial cells, where RSV replication induces potent expression of chemokines, the epithelium is postulated to be a primary initiator of pulmonary inflammation in RSV infection. The spectrum of RSV-induced chemokines expressed by alveolar epithelial cells has not been fully investigated. In this report, we profile the kinetics and patterns of chemokine expression in RSV-infected lower airway epithelial cells (A549 and SAE). In A549 cells, membrane-based cDNA macroarrays and high-density oligonucleotide probe-based microarrays identified inducible expression of CC (I-309, Exodus-1, TARC, RANTES, MCP-1, MDC, and MIP-1 alpha and -1 beta), CXC (GRO-alpha, -beta, and -gamma, ENA-78, interleukin-8 [IL-8], and I-TAC), and CX(3)C (Fractalkine) chemokines. Chemokines not previously known to be expressed by RSV-infected cells were independently confirmed by multiprobe RNase protection assay, Northern blotting, and reverse transcription-PCR. High-density microarrays performed on SAE cells confirmed a similar pattern of RSV-inducible expression of CC chemokines (Exodus-1, RANTES, and MIP-1 alpha and -1 beta), CXC chemokines (I-TAC, GRO-alpha, -beta, and -gamma, and IL-8), and Fractalkine. In contrast, TARC, MCP-1, and MDC were not induced, suggesting the existence of distinct genetic responses for different types of airway-derived epithelial cells. Hierarchical clustering by agglomerative nesting and principal-component analyses were performed on A549-expressed chemokines; these analyses indicated that RSV-inducible chemokines are ordered into three related expression groups. These data profile the temporal changes in expression by RSV-infected lower airway epithelial cells of chemokines, chemotactic proteins which may be responsible for the complex cellular infiltrate in virus-induced respiratory inflammation.
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PMID:Expression of respiratory syncytial virus-induced chemokine gene networks in lower airway epithelial cells revealed by cDNA microarrays. 1153 68

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

We previously reported that chronic stimulation with low, noncytotoxic doses of extracellular adenosine triphosphate (ATP) induced a distorted maturation of dendritic cells (DCs) and impaired their capacity to initiate T-helper (Th) 1 responses in vitro. Here, we examined the effects of ATP on chemokine-receptor expression and chemokine production by DCs. ATP strongly induced expression of CXC chemokine receptor 4 on both immature and lipopolysaccharide (LPS)-stimulated DCs and slightly up-regulated CC chemokine receptor (CCR) 7 on both DC types. In contrast, ATP reduced CCR5 expression on immature DCs. These effects were confirmed at both the messenger RNA and protein levels and were not produced by uridine triphosphate (UTP). Consistent with the changed receptor expression, ATP increased migration and intracellular calcium of immature and mature DCs to stromal-derived factor 1 (CXC ligand [CXCL] 12) and macrophage inflammatory protein [MIP] 3 beta (CC ligand [CCL] 19), whereas responses to MIP-1 beta (CCL4) were reduced. DCs are an important source of chemokines influencing recruitment of distinct T-lymphocyte subsets. ATP, but not UTP, significantly reduced LPS-induced production of interferon-inducible protein 10 (CXCL10) and regulated upon activation, normal T-cell expressed and secreted chemokine (CCL5); increased secretion of macrophage-derived chemokine (CCL22); and did not change production of thymus and activation-regulated chemokine (CCL17). Consistent with these findings, supernatants from ATP-treated mature DCs attracted Th1 and T-cytotoxic 1 cells less efficiently, whereas migration of Th2 and T cytotoxic 2 cells was not affected. Our data suggest that ATP provides a signal for enhanced lymph node localization of DCs but that it may, at the same time, diminish the capacity of DCs to amplify type 1 immune responses.
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PMID:Dendritic cells exposed to extracellular adenosine triphosphate acquire the migratory properties of mature cells and show a reduced capacity to attract type 1 T lymphocytes. 1186 Dec 88

Natural killer T (NKT) cells are important regulators of the immune system, but their trafficking machinery, including expression of chemokine receptors, has been poorly defined. Unlike other conventional T-cell populations, we show that most NKT cells express receptors for extralymphoid tissue or inflammation-related chemokines (CCR2, CCR5, and CXCR3), while few NKT cells express lymphoid tissue-homing chemokine receptors (CCR7 and CXCR5). A population with homing potential for lymph nodes (L selectin(+) CCR7(+)) exists only within a small subset of CD4 NKT cells. We show differential expression of chemokine receptors among NKT cell subsets: CCR4 is mainly expressed by a high cytokine (interleukin-4/interleukin-2)-producing (CD4) NKT subset, while CCR1, CCR6, and CXCR6 are preferentially expressed by the low cytokine-producing CD8 and CD4(-)CD8(-) subsets. In line with this, TARC/CCL17 (a CCR4 ligand) induces preferential chemotaxis of the CD4 NKT subset, while chemotactic activities of LARC/CCL20 (a CCR6 ligand) and MIP-1 alpha/CCL3 (a CCR1 ligand) are focused on the CD8 and CD4(-)CD8(-) NKT cells. We conclude that, unlike conventional naive, memory, or effector T cells, the entire NKT cell population expresses nonlymphoid tissue homing chemokine receptors, yet NKT cell subsets differ considerably from each other by displaying distinct and reciprocal expression patterns of some chemokine receptors. Our results identify chemokine receptors that are potentially important for trafficking of human blood NKT cell subsets and reveal their function (cytokine production capacity)-dependent differential trafficking potentials.
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PMID:Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among V alpha 24(+)V beta 11(+) NKT cell subsets with distinct cytokine-producing capacity. 1207 1

Although adjuvants are essential for the initiation of experimental autoimmune diseases, their precise contribution to the pathological manifestations is still poorly understood. Experimental autoimmune thyroiditis (EAT) is interesting in that respect because it can be initiated with the help of two different adjuvants Freund's complete or LPS which may initiate independent pathogenic pathways. In the present study, we have compared Freund's-induced versus LPS-induced EAT with respect to their dependence upon CD8+ T cells, which are considered as major actors in the pathogenesis of thyroiditis. Our results reveal that whereas CD8+ T cells are mandatory in the Freund's model, they can be bypassed in the LPS model. On the basis of this finding, we have examined the possibility that LPS may act directly upon in vitro cultured thyrocytes with no intermediate cell stages. Indeed, LPS triggers transcription and protein synthesis of several chemokines such as MIP-3alpha, RANTES, MCP-1 or TARC. Thus, beside enhancing the immunogenicity of autoantigens, probably via antigen trafficking and presentation, adjuvants such as LPS directly interact with the target organ through synthesis and release of powerful T cell attractants that facilitate its lymphocytic infiltration.
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PMID:LPS and Freund's adjuvant initiate different inflammatory circuits in experimental autoimmune thyroiditis. 1279 14

Dendritic cells (DC) are potent antigen - presenting cells that can orientate the immune response towards a Th1 or a Th2 type. DC produce chemokines that are involved in the recruitment of either Th1 cells, such as IP10 (CXCL10), Th2 cells such as TARC (CCL17) and MDC (CCL22), or non-polarized T cells such as RANTES (CCL5) and MIP-lalpha (CCL3). We investigated whether monocyte-derived DC (MD-DC) generated from healthy donors or from patients sensitive to Dermatophagoides pteronyssinus (Dpt) and exposed to the cysteine-protease Der p 1(allergen of Dpt), could upregulate the expression of chemokines involved in type 1 or type 2 T cell recruitment. MD-DC were pulsed with either Der p 1 or with LPS as the control and the chemokines produced were evaluated using ELISA and chemotaxis assays. Der p 1-pulsed DC from allergic patients showed increased TARC (CCL17) and MDC (CCL22) production without modifying IP-10 (CXCL10) release. Der p 1-pulsed DC from healthy donors showed only increased IP-10 (CXCL10) secretion. RANTES (CCL5) and MIP-lalpha (CCL3) production were similarly increased when DC were from healthy or allergic donors. The selective Th2 clone recruitment activity of supernatants from Der p 1-pulsed DC of allergic patients was inhibited by anti-TARC (CCL17) and anti-MDC (CCL22) neutralizing Abs. By using anti-IP10 (CXCL10) blocking Abs, supernatants of Der p 1-pulsed DC from healthy donors were shown to be involved in the recruitment of Th1 cells. These results suggest that in allergic patients exposed to house dust mites, DC may favour the exacerbation of the Th2 response via the increase in type 2 chemokine production.
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PMID:Monocyte-derived dendritic cells exposed to Der p 1 allergen enhance the recruitment of Th2 cells: major involvement of the chemokines TARC/CCL17 and MDC/CCL22. 1471 13

Chemokines are likely to play important roles in the pathophysiology of diseases associated with Epstein-Barr virus (EBV). Here, we have analyzed the repertoire of chemokines expressed by EBV-infected B cells. EBV infection of B cells induced expression of TARC/CCL17 and MDC/CCL22, which are known to attract Th2 cells and regulatory T cells via CCR4, and also upregulated constitutive expression of MIP-1 alpha/CCL3, MIP-1 beta/CCL4, and RANTES/CCL5, which are known to attract Th1 cells and cytotoxic T cells via CCR5. Accordingly, EBV-immortalized B cells secreted these chemokines, especially CCL3, CCL4, and CCL22, in large quantities. EBV infection or stable expression of LMP1 also induced CCL17 and CCL22 in a B-cell line, BJAB. The inhibitors of the TRAF/NF-kappa B pathway (BAY11-7082) and the p38/ATF2 pathway (SB202190) selectively suppressed the expression of CCL17 and CCL22 in EBV-immortalized B cells and BJAB-LMP1. Consistently, transient-transfection assays using CCL22 promoter-reporter constructs demonstrated that two NF-kappa B sites and a single AP-1 site were involved in the activation of the CCL22 promoter by LMP1. Finally, serum CCL22 levels were significantly elevated in infectious mononucleosis. Collectively, LMP1 induces CCL17 and CCL22 in EBV-infected B cells via activation of NF-kappa B and probably ATF2. Production of CCL17 and CCL22, which attract Th2 and regulatory T cells, may help EBV-infected B cells evade immune surveillance by Th1 cells. However, the concomitant production of CCL3, CCL4, and CCL5 by EBV-infected B cells may eventually attract Th1 cells and cytotoxic T cells, leading to elimination of EBV-infected B cells at latency III and to selection of those with limited expression of latent genes.
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PMID:Selective induction of Th2-attracting chemokines CCL17 and CCL22 in human B cells by latent membrane protein 1 of Epstein-Barr virus. 1474 32

Dendritic cells (DCs) and chemokines are important in linking innate and adaptive immunity. We previously reported that Fas ligation induced interleukin 1beta (IL-1beta)-dependent maturation and IL-1beta-independent survival of DCs, with extracellular signal-regulated kinase (ERK) and nuclear factor-kappaB (NF-kappaB) signaling pathways involved, respectively. We describe here that Fas ligation induced DCs to rapidly produce both CXC and CC chemokines, including macrophage inflammatory protein 2 (MIP-2), MIP-1alpha, MIP-1beta, monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated on activation normal T cell expressed and secreted), and TARC (thymus and activation-regulated chemokine), resulting in enhanced chemoattraction of neutrophils and T cells by Fas-ligated DCs in vivo or by its supernatant in vitro. These chemokines work synergistically in chemoattraction of neutrophils and T cells with MIP-2 more important for neutrophils, MIP-1alpha and TARC more important for T cells. Moreover, Fas-ligated DCs increased endocytosis by neutrophils and activation and proliferation of antigen-specific naive T cells. Fas ligation-induced DC secretion of chemokines involves Ras/Raf/mitogen-activated protein kinase kinase (MEK)/ERK activation and is ERK, but not NF-kappaB, dependent. Activation of caspases, including caspase 1, but not IL-1 autocrine action, is involved in this process. These data indicate that Fas signaling provides a key link between innate response and adaptive immunity by promoting DC chemokine production.
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PMID:Fas signal links innate and adaptive immunity by promoting dendritic-cell secretion of CC and CXC chemokines. 1594 11


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