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)

DC function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led to the investigation of the chemokine responsiveness of DC during their development and maturation. These studies have shown that immature and mature DC are not recruited by the same chemokines. Immature DC respond to many CC- and CXC-chemokines (MIP-1alpha, MIP-1beta, MIP-5, MCP-3, MCP-4, RANTES, TECK, and SDF-1) and in particular to MIP-3alpha/LARC, which acts through CCR6, a receptor mainly expressed in DC and lymphocytes. Like most other chemokines acting on immature DC, MIP-3alpha is inducible on inflammatory stimuli. In contrast, mature DC have lost their responsiveness to most of these chemokines through receptor down-regulation or desensitization, but acquired responsiveness to MIP-3beta/ELC and 6Ckine/SLC as a consequence of CCR7 up-regulation. MIP-3alpha mRNA is only detected within inflamed epithelial crypts of tonsils, the site of antigen entry known to be infiltrated by immature DC, whereas MIP-3alpha and 6Ckine are specifically expressed in the T cell-rich areas where mature IDC home. These observations suggest a role for chemokines induced on inflammation such as MIP-3alpha in recruitment of immature DC at the site of injury and a role for MIP-3beta/6Ckine in accumulation of antigen-loaded mature DC in T cell-rich areas of the draining lymph node. A better understanding of the regulation of DC trafficking might offer new opportunities of therapeutic interventions to suppress or stimulate the immune response.
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PMID:Regulation of dendritic cell trafficking: a process that involves the participation of selective chemokines. 1044 63

Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue and play important roles in disease processes. Among the biologic activities of chemokines is inhibition of proliferation of normal hematopoietic progenitors. However, chemokines that inhibit normal progenitors rarely inhibit proliferation of hematopoietic progenitors from patients with chronic myelogenous leukemia (CML). We and others recently cloned a subfamily of CC chemokines that share similar amino-terminal peptide sequences and a remarkable ability to chemoattract T cells. These chemokines, Exodus-1/LARC/MIP-3alpha, Exodus-2/SLC/6Ckine/TCA4, and Exodus-3/CKbeta11/MIP-3beta, were found to inhibit proliferation of normal human marrow progenitors. The study described here found that these chemokines also inhibited the proliferation of progenitors in every sample of marrow from patients with CML that was tested. This demonstration of consistent inhibition of CML progenitor proliferation makes the 3 Exodus chemokines unique among chemokines. (Blood. 2000;95:1506-1508)
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PMID:The exodus subfamily of CC chemokines inhibits the proliferation of chronic myelogenous leukemia progenitors. 1066 33

Natural killer (NK) cells play an important role in innate and adaptive immune responses to obligate intracellular pathogens. Nevertheless, the regulation of NK cell trafficking and migration to inflammatory sites is poorly understood. Exodus-1/MIP-3alpha/LARC, Exodus-2/6Ckine/SLC, and Exodus-3/MIP-3beta/ELC/CKbeta-11 are CC chemokines that share a unique aspartate-cysteine-cysteine-leucine motif near their amino terminus and preferentially stimulate the migration of T lymphocytes. The effects of Exodus chemokines on human NK cells were examined. Exodus-1, -2, and -3 did not induce detectable chemotaxis of resting peripheral blood NK cells. In contrast, Exodus-2 and -3 stimulated migration of polyclonal activated peripheral blood NK cells in a dose-dependent fashion. Exodus-2 and -3 also induced dose-dependent chemotaxis of NKL, an IL-2-dependent human NK cell line. Results of modified checkerboard assays indicate that migration of NKL cells in response to Exodus-2 and -3 represents true chemotaxis and not simply chemokinesis. Exodus-1, -2, and -3 did not induce NK cell proliferation in the absence of other stimuli. Nevertheless, Exodus-2 and -3 significantly augmented IL-2-induced proliferation of normal human CD56(dim) NK cells. In contrast, Exodus-1, -2, and -3 did not affect the cytolytic activity of resting or activated peripheral blood NK cells. Expression of message for CCR7, a shared receptor for Exodus-2 and -3, was detected in activated polyclonal NK cells and NKL cells but not resting NK cells. Taken together, these results indicate that Exodus-2 and -3 can participate in the recruitment and proliferation of activated NK cells. Exodus-2 and -3 may regulate interactions between T cells and NK cells that are crucial for the generation of optimal immune responses.
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PMID:Regulation of human natural killer cell migration and proliferation by the exodus subfamily of CC chemokines. 1067 70

DC (dendritic cells) represent an heterogeneous family of cells which function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. Then, following inflammatory stimuli, they leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. The key role of DC migration in their sentinel function led to the investigation of the chemokine responsiveness of DC populations during their development and maturation. These studies have shown that immature DC respond to many CC and CXC chemokines (MIP-1 alpha, MIP-1 beta, MIP-3 alpha, MIP-5, MCP-3, MCP-4, RANTES, TECK and SDF-1) which are inducible upon inflammatory stimuli. Importantly, each immature DC population displays a unique spectrum of chemokine responsiveness. For examples, Langerhans cells migrate selectively to MIP-3 alpha (via CCR6), blood CD11c+ DC to MCP chemokines (via CCR2), monocytes derived-DC respond to MIP-1 alpha/beta (via CCR1 and CCR5), while blood CD11c- DC precursors do not respond to any of these chemokines. All these chemokines are inducible upon inflammatory stimuli, in particular MIP-3 alpha, which is only detected within inflamed epithelium, a site of antigen entry known to be infiltrated by immature DC. In contrast to immature DC, mature DC lose their responsiveness to most of these inflammatory chemokines through receptor down-regulation or desensitization, but acquire responsiveness to ELC/MIP-3 beta and SLC/6Ckine as a consequence of CCR7 up-regulation. ELC/MIP-3 beta and SLC/6Ckine are specifically expressed in the T-cell-rich areas where mature DC home to become interdigitating DC. Altogether, these observations suggest that the inflammatory chemokines secreted at the site of pathogen invasion will determine the DC subset recruited and will influence the class of the immune response initiated. In contrast, MIP-3 beta/6Ckine have a determinant role in the accumulation of antigenloaded mature DC in T cell-rich areas of the draining lymph node, as illustrated by recent observations in mice deficient for CCR7 or SLC/6Ckine. A better understanding of the regulation of DC trafficking might offer new opportunities of therapeutic interventions to suppress, stimulate or deviate the immune response.
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PMID:Dendritic cell biology and regulation of dendritic cell trafficking by chemokines. 1115 41

Chemokine-chemokine receptor interaction plays an essential role in leukocyte/dendritic cell (DC) trafficking in inflammation and immune responses. We investigated the pathophysiological roles of secondary lymphoid tissue chemokine (SLC; CCL21) and macrophage inflammatory protein-2 (MIP-2) in the development of acute pulmonary inflammation induced by an intratracheal injection of Propionibacterium acnes in mice. Immunohistochemical studies revealed that SLC was constitutively expressed in the peribronchial areas and perivascular lymphatics in normal mice. MIP-2-positive cells were observed in alveolar spaces in mice challenged with P. acnes. Both neutralization Abs against MIP-2 and CXC chemokine receptor 2 alleviated the P. acnes-induced pulmonary inflammation when injected before P. acnes Ag challenge. On the other hand, polyclonal anti-SLC Abs (pAbs) exacerbated the pulmonary inflammation. The numbers of mature DCs (MHC class II +, CD11c+, and CD86+) as well as macrophages and neutrophils in the P. acnes Ag-challenged lungs were increased, whereas the number of CD4+ T cells, including memory T cells, was decreased. The numbers of mature and proliferating CD4+ T cells (bromodeoxyuridine(+)CD4+) in regional lymph nodes were decreased in mice injected with anti-SLC pAbs compared with those in mice treated with control Abs. An in vitro proliferation assay confirmed the impairment of the Ag-specific T cell response in regional lymph nodes of mice treated with anti-SLC pAbs. These results indicate for the first time a regulatory role for SLC-recruited mature DCs in bridging an acute inflammatory response (innate immunity) and acquired immunity in the lung.
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PMID:Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation. 1116 Feb 58

A growing body of evidence suggests that mammalian ovulation bears similarities to local inflammatory reactions. Monocytes/macrophages, eosinophils, and neutrophils are known to infiltrate the area surrounding the dominant follicle before ovulation. Candidate local chemoattractants may include a family of small cytokines, also known as chemokines. In the present study, quantitative RT-PCR was used to initially identify and quantify the chemokines expressed in the preovulatory rat ovary. The chemokines monocyte chemotatic protein 1 (MCP-1), MCP-3, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, MIP-1gamma, regulated upon activation normal T cell expressed and secreted, eotaxin, interferon-inducible protein of 10 kDa, growth-regulated oncogene, lymphotactin, and fractalkine were all expressed in the PMSG-primed rat ovary 6 h post human CG. C10, T cell activation gene 3, exodus, exodus-2, cytokine-induced neutrophil chemoattractant-2, MIP-2, and lipopolysaccharide-induced C-X-C were not expressed in the PMSG-primed rat ovary 6 h post human CG. The cyclic variation of the ovary-positive chemokines was also evaluated throughout the course of a superovulated ovarian cycle. Significant preovulatory up-regulation relative to the untreated control state was documented for MCP-1 (18-fold), MCP-3 (12-fold), and growth-regulated oncogene (25-fold). In contrast, the preovulatory ovarian expression of eotaxin, fractalkine and regulated upon activation normal T cell expressed and secreted was not increased. These observations suggest that intraovarian chemokines may be responsible for the cyclic intraovarian residence of representatives of the white blood cell series.
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PMID:Expression, hormonal regulation, and cyclic variation of chemokines in the rat ovary: key determinants of the intraovarian residence of representatives of the white blood cell series. 1186 98

The lymphotoxin-beta receptor (LTbetaR) plays critical roles in inflammation and lymphoid organogenesis through activation of NF-kappaB. In addition to activation of the classical NF-kappaB, ligation of this receptor induces the processing of the cytosolic NF-kappaB2/p100 precursor to yield the mature p52 subunit, followed by translocation of p52 to the nucleus. This activation of NF-kappaB2 requires NIK and IKKalpha, while NEMO/IKKgamma is dispensable for p100 processing. IKKbeta-dependent activation of canonical NF-kappaB is required for the expression but not processing of p100 and for the expression of proinflammatory molecules including VCAM-1, MIP-1beta, and MIP-2 in response to LTbetaR ligation. In contrast, IKKalpha controls the induction by LTbetaR ligation of chemokines and cytokines involved in lymphoid organogenesis, including SLC, BLC, ELC, SDF1, and BAFF.
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PMID:The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. 1238 45

Dendritic cells (DCs) are potent antigen-presenting cells that likely play multiple roles in human immunodeficiency virus type 1 (HIV-1) pathogenesis. We used the simian immunodeficiency virus (SIV)/macaque model to study the effects of infection on homeostatic chemokine expression and DC localization directly in secondary lymphoid tissues. SIV infection altered the expression of chemokines (CCL19/MIP-3beta, CCL21/ 6Ckine, and CCL20/MIP-3alpha) and of chemokine receptors (CCR7 and CCR6) that drive DC trafficking. CCL19/MIP-3beta, CCL20/MIP-3alpha, CCR6, and CCR7 expression increased in lymph nodes during the early systemic burst of viral replication (acute infection), whereas CCL21/6Ckine expression progressively decreased throughout disease to AIDS. Parallel with the SIV-induced perturbations in chemokine expression were changes in the expression of the DC-associated markers, DC-SIGN, DC-LAMP, and DECTIN-1. During AIDS, DC-LAMP mRNA expression levels were significantly reduced in lymph nodes and spleen, and DC-SIGN levels were significantly reduced in spleen. These findings suggest that the disruption of homeostatic chemokine expression is responsible, in part, for alterations in the networks of antigen-presenting cells in lymphoid tissues, ultimately contributing to systemic immunodeficiency.
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PMID:Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo. 1240 87

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

Although production of chemokines by vascular endothelial cells has been documented, there is only limited information regarding the expression of chemokines by the lymphatic endothelium. Here we used lymphatic endothelial cells (LEC) derived from experimentally induced murine lymphangiomas to investigate the pattern of chemokine expression by these cells. Histological analysis of the lymphatic hyperplasia revealed the presence of leucocytes in the tissues surrounding the lesions, suggesting the presence of chemoattractant activity. A functional chemotactic assay on human polymorphonuclear cells and on purified subpopulations of murine leucocytes using culture supernatants from LEC primary cultures confirmed the presence of chemoattractant activity. The identity of different cytokines of the CXC, CC and C subfamilies was investigated by reverse trancriptase-polymerase chain reaction on total endothelial cell RNA. Amplified fragments corresponding to KC, IP10, Mig-1, BCL, MIP-2, SLC, RANTES, MCP-1, C10, and Lptn were obtained, and confirmed by Southern blot and sequencing. In contrast, MIP-1alpha, MIP-1beta, and MIP-1gamma were not detected. Higher levels of expression were revealed by Northern blot analysis for Mig-1, MCP-1 and C10. The lymphatic endothelium-restricted production of these chemokines was also confirmed by in situ hybridization. The presence of high C10 mRNA expression levels in LEC was particularly unexpected, because the production of this molecule has been previously identified only in cells of the haematopoietic lineage. These observations represent the first detailed analysis of chemokine production by lymphatic endothelial cells and may account, in part, for the mechanism of leucocyte recruitment into the lymphatics, and of lymphocyte recirculation within the lymphatic system.
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PMID:Evidence of CXC, CC and C chemokine production by lymphatic endothelial cells. 1266 14


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