Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Burkitt's lymphoma receptor 1 (BLR1) identified initially in Burkitt lymphoma cells has been the first member of the superfamily of G-protein-coupled receptors with a lymphocyte specific expression pattern. BLR1 shows significant relationship to receptors for chemokines (IL-8, MIP-1 beta) and neuropeptides. The gene encoding the murine homologue of the human BLR1 receptor was isolated and used to study its tissue-specific expression. Blr-1 consists of two exons encoding a protein of 374 amino acid residues which shows 83% identity with the human homologue. Screening of normal tissues of adult BALB/c mice revealed that blr-1-specific RNA is detected consistently at low levels in secondary lymphatic organs. The blr-1 gene is expressed regularly and strongly in lymphomas of mature B cells but not in plasmacytomas. SCID mice deficient in the development of mature B cells have strongly reduced levels of blr-1-specific RNA in the spleen. Cytokine mediated induction (IL4, IL6) of terminal differentiation of resting B cells towards Ig-secreting plasma cells completely downregulates expression of blr-1. RNA in situ hybridization using brain sections demonstrates blr 1 transcription in the granule and Purkinje cell layer of the cerebellum. The precise delineation of the restricted expression pattern of the blr-1 gene will support the identification of its ligand and may provide a clue to understand how BLR1 exerts its biological function within the immune and nervous system.
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PMID:Selective expression of the murine homologue of the G-protein-coupled receptor BLR1 in B cell differentiation, B cell neoplasia and defined areas of the cerebellum. 792 Jan 82

The responses of lymphocytes to six CC chemokines--MCP-1, MCP-2, MCP-3, MIP-1 alpha, MIP-1 beta, and RANTES--were studied using cloned human CD4+ and CD8+ T cells. All CC chemokines tested induced migration of both types of lymphocytes, whereas two CXC chemokines used as controls, IL-8 and IP-10, were inactive. The monocyte chemotactic proteins (MCP-1, MCP-2, and MCP-3) showed a typically bimodal concentration dependence, and were considerably more effective than MIP-1 alpha, MIP-1 beta, or RANTES. All CC chemokines also induced a rapid and transient rise in cytosolic free Ca2+ in either type of T cell. The rise was prevented by Bordetella pertussis toxin treatment, indicating that G-protein-coupled receptors are involved in signaling. It was most pronounced with MCP-1 and MCP-3, which is in agreement with the efficacy of these chemokines as chemoattractants. The responses to MCP-2, MIP-1 alpha, MIP-1 beta, and RANTES were weaker, and no changes were obtained on stimulation with IL-8 or IP-10. Freshly isolated human blood lymphocytes were also tested, but neither migration nor Ca2+ changes were observed. Low numbers of high-affinity receptors for MCP-1 were found on CD4+ and CD8+ cells ( < 900 per cell, Kd < 1 nM), and desensitization experiments showed that MCP-1, MCP-2, and MCP-3 share receptors. Owing to their superior effectiveness on CD4+ and CD8+ T cells, the monocyte chemotactic proteins could play a major role in the recruitment of activated T lymphocytes.
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PMID:Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes. 792 71

The pX gene of human T-cell leukemia virus type I (HTLV-I) is known to be a potent transactivator of the viral gene and the host genes which are important for cell proliferation in vitro. It has been reported that various diseases occur in transgenic mice harboring either tax, pX, or env-pX gene, such as mesenchymal tumor, neurofibroma, thymic atrophy, muscle degeneration, exocrinopathy and arthropathy. We previously demonstrated that rat but not mouse CD4 positive T cells could be easily infected and immortalized by HTLV-I and infectious transmission of HTLV-I induced HAM/TSP-like myelopathy in WKAH rats after long incubation periods of 16 months. These observations prompted us to produce a series of transgenic rats that expressed the pX gene products under the control of mouse H-2Kd promotor in order to evaluate further the biological and pathological function of the pX gene in vivo. In various tissues of pX transgenic rats (pX rats), pX mRNA was constitutively expressed irrespective of age. PX rats developed mammary tumors with massive infiltration by neutrophils as early as 9 months of age. Pathological and immunohistochemical examination revealed that the tumors were undifferentiated carcinomas of the mammary gland origin. They were transplantable into pX rats, but not into normal syngenic rats. High levels of mRNA expression of not only the pX transgene but also the host genes such as Gro (melanoma growth-stimulatory activity/KC), MIP-2 (macrophage inflammatory protein-2) and IL-1 alpha were demonstrated in the tumor tissues. Gro and MIP-2 which were known as IL-8 families were likely to be produced by tumor cells and appeared to be responsible for neutrophil infiltration in the tumor tissues. Lastly, pX rats described here appear to be suitable animal models for elucidating mechanisms involved in the tumorigenesis and the transactivation of the cellular genes by HTLV-I, especially by the pX gene products in vivo.
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PMID:[Pathological and molecular analyses of mammary tumors induced in HTLV-I pX transgenic rats]. 792 76

The murine beta-chemokine TCA3 was purified to homogeneity. The biologic activities of the purified glycoprotein were evaluated in vivo and in vitro. Mice injected i.p. with 1- to 100-ng purified rTCA3 exhibited a rapid influx of neutrophils and macrophages. Increased numbers of neutrophils and monocytes were observed in peripheral blood within 15 min and peak at 45 min. After 45 min neutrophil and macrophage levels were increased in the peritoneal exudate with peak levels occurring at 2 h, followed by a subsequent decline by 24 h. Inflammatory responses were induced in a dose-dependent fashion. The in vivo inflammatory responses were mirrored by the pattern of TCA3-induced chemotaxis in vitro. Neutrophils and macrophages responded to similar concentrations of TCA3 (3 x 10(-9) to 10(-8) M). Lymph node cells responded to other chemokines but did not migrate to TCA3. We also demonstrated that rTCA3 stimulates a transient increase in cytoplasmic free calcium in monocytic cells through a PTX-sensitive pathway. Cross-desensitization studies indicate that TCA3 acts independently of other beta-chemokines (MIP-1 alpha and RANTES) and the alpha-chemokine IL-8. Furthermore, TCA3 does not induce a Ca2 lux in cells transfected with cDNA for the C-C CKR-1 chemokine receptor, supporting the conclusion that there are distinct receptors for TCA3.
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PMID:Biologic activities of the murine beta-chemokine TCA3. 796 34

Macrophage inflammatory protein 1 alpha (MIP-1 alpha), a monocyte cytokine, has roles postulated for it in neutrophil chemoattraction, the inflammatory response and the control of haemopoietic stem cell proliferation. The three-dimensional structure of MIP-1 alpha has been modelled structurally, based on its sequence similarity to interleukin-8 and related proteins. The predicted dimeric form of MIP-1 alpha contains two symmetry-related antiparallel alpha-helices lying at an angle across a beta-sheet. The interhelical region and the beta-sheet flooring it are discussed as the potential receptor-binding site in terms of the distribution of negatively charged amino-acid side-chains, which contrasts remarkably with the corresponding positively-charged locations for IL-8. The general topographical features of this (alpha + beta) structural family of cytokines and related proteins (including HLA-A2, PF-4) are discussed. The members of this cytokine family fall into two structural groups as the antiparallel helices (N to C directed) mounted across the beta-sheet platform can be located in a clockwise (e.g. HLA-A2) or anticlockwise (e.g. MIP-1 alpha) sense with respect to the beta-floor).
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PMID:A homology-derived structural model of the murine macrophage inflammatory protein, MIP-1 alpha. 806 19

The chemokines are a family of immune mediators involved in a wide range of inflammatory processes, most importantly as chemoattractants of monocytes, neutrophils, lymphocytes, and fibroblasts to sites of inflammation. Nuclear magnetic resonance and x-ray crystallographic studies have shown that IL-8 and macrophage-inflammatory protein-1 beta (MIP-1 beta) form noncovalent dimers and that platelet factor-4 (PF-4) forms noncovalent dimers and tetramers, leading to the assumption that, as a family, the chemokines would form multimeric structures. In this study, we analyze the association states of the chemokines IL-8, monocyte chemoattractant protein-1 (MCP-1), and I-309, by using a combination of size exclusion HPLC, sedimentation equilibrium ultracentrifugation, and chemical cross-linking. We find that the association states of MCP-1 and IL-8 are characterized by an equilibrium between monomers and dimers: although dimers predominate at concentrations above 100 microM, these chemokines are almost exclusively monomeric at the nanomolar concentrations at which they display maximal chemotactic activity. I-309, by contrast, remains a monomer at all concentrations tested. I-309 contains two additional cysteine residues (C26 and C68) that are not found in any other members of the chemokine family. We used cyanogen bromide and trypsin digestion strategies to demonstrate that these two residues are linked in a unique intramolecular disulfide bond. Furthermore, by using site-directed mutagenesis, we show that the integrity of this bond is crucial for protein secretion.
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PMID:The chemokines IL-8, monocyte chemoattractant protein-1, and I-309 are monomers at physiologically relevant concentrations. 807 76

Chemokines are a superfamily of structurally related cytokines involved in leukocyte recruitment in normal and neoplastic tissues. The availability of non-cross-reacting reagents specific for each member of the C-C and C-X-C family is important for careful characterization of their in vitro and in vivo production and relevance. Here we describe a novel, highly specific, mAb against monocyte chemotactic protein-1 (MCP-1). The 5D3-F7 mAb (IgG1,kappa) recognizes human recombinant and natural MCP-1 in ELISA, immunoprecipitation and immunoblot analysis. As a source of natural MCP-1 we used the 8387 human sarcoma line which produces spontaneously MCP-1 and responds to TNF with increased expression and release. The 5D3-F7 mAb inhibited the chemotactic activity of MCP-1 for monocytes. Using the 5D3-F7 mAb and a polyclonal rabbit anti-MCP-1 serum, a sandwich ELISA was developed. In both the direct and the sandwich ELISA, the 5D3-F7 mAb recognized human MCP-1, but not the closely related C-C chemokines MCP-1, MCP-2, MCP-3, MIP-1 alpha, and RANTES and the C-X-C chemokines IL-8, gro alpha and NAP-2. In culture supernatants the sensitivity of the sandwich ELISA was approximately equal to 30 pg/ml. The sandwich ELISA permitted detection of MCP-1 in resting or cytokine-stimulated endothelial, mesothelial and Kaposi's sarcoma cells. Preliminary immunohistochemical analysis revealed production of MCP-1 by macrophage-like cells at sites of inflammation. The 5D3-F7 mAb provides a novel, highly specific reagent with which to investigate the in vitro and in vivo production and role of MCP-1.
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PMID:A new monoclonal antibody (5D3-F7) which recognizes human monocyte-chemotactic protein-1 but not related chemokines. Development of a sandwich ELISA and in situ detection of producing cells. 808 29

In this study, we examined IL-10 regulation of polymorphonuclear leukocyte (PMN)-derived chemokine expression. Studies demonstrated that IL-10 dose dependently suppressed the expression and production of PMN-derived macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, IL-8 mRNA, and protein. Although inhibition of protein synthesis was found to superinduce the expression of PMN-derived chemokine steady-state mRNA, the inhibitory activity of IL-10 was completely abrogated in the presence of either cycloheximide or puromycin. These data suggest that the effect of IL-10 on PMN-derived chemokine expression was through the production of de novo repressor protein(s). Next, we examined the half-life (t1/2) of chemokine mRNA by LPS-treated PMNs in the presence or absence of IL-10. The t1/2 of MIP-1 alpha, MIP-1 beta, and IL-8 mRNA from PMNs treated for 4 h with LPS before actinomycin-D (Ac-D) addition were approximately 40 min, 1.7 h, and 2 h, respectively, whereas the t1/2 from PMNs stimulated for 8 h before Ac-D were 2, 2, and > 9 h, respectively. Interestingly, IL-10 significantly accelerated the decay of all three of the above chemokine mRNA. The t1/2 of MIP-1 alpha, MIP-1 beta, and IL-8 mRNA from PMNs treated with LPS plus IL-10 compared with LPS alone was reduced by 62, 50, and 40%, respectively, at the 4-h time point and by 50, 25, and 70%, respectively, at the 8-h time point. These findings support the notion that PMNs are an important cellular source of both C-X-C and C-C chemokines, and that IL-10 regulates both inflammatory/immune responses by not only modulating the activities of T cell, B cell, and mononuclear phagocyte function, but also by inhibiting PMN-derived chemokine expression.
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PMID:Regulation of neutrophil-derived chemokine expression by IL-10. 814 35

CC chemokines are small inducible proteins that are related to interleukin 8. Recent studies have shown that several CC chemokines, MCP-1, MCP-3, RANTES and MIP-1 alpha, act on basophils and/or eosinophils via GTP-binding protein-coupled receptors. Marco Baggiolini and Clemens Dahinden discuss the involvement of CC chemokines in the recruitment and activation of the main effector cells of allergic inflammation.
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PMID:CC chemokines in allergic inflammation. 817 45

Previous studies have shown that during the development of a mixed lymphocyte reaction (MLR) levels of the chemotactic cytokines IL-8 and MCP-1 (members of the C-X-C and C-C supergene families, respectively) increase in a time-dependent fashion, and that the production of these chemokines correlates with the magnitude of responsiveness to alloantigen. Furthermore, the responsiveness to alloantigen in the context of a MLR has been shown to be regulated by the oxidative metabolism of L-arginine. We postulated that competitive antagonism of the L-arginine metabolic pathway in a human MLR may alter the production of members of the C-C and C-X-C chemokine families. To test this hypothesis, mononuclear cells were isolated from healthy individuals and subjected to a one-way MLR in the presence or absence of varying concentrations of an L-arginine competitive inhibitor, NG-methyl-L-arginine (NMA: 50 to 500 microM). When the MLR was performed in the presence of NMA (500 microM), the production of IL-8 increased twofold (P < 0.05) and ENA-78 increased fivefold (P < 0.05), while MCP-1 and MIP-1 alpha were not significantly altered. These findings suggest that NMA, an inhibitor of the L-arginine metabolic pathway, may regulate the production of specific C-X-C chemokines, IL-8 and ENA-78, during a MLR. In contrast, the production of MCP-1 and MIP-1 alpha, members of the C-C chemokine family, does not appear to be regulated by this inhibitor of the oxidative metabolism of L-arginine in the context of a MLR.
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PMID:Regulation of chemokine production by the oxidative metabolism of L-arginine in a human mixed lymphocyte reaction. 820 45


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