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)

Chemokines are cytokines which induce chemotaxis on many cell types, thus regulating cell migration within inflammatory and allergic sites, and leucocyte homing. Also, they play a crucial role in inflammatory and tumor-associated angiogenesis, as well as in tumor progression. Chemokines are grouped into: 1) alpha or CXC; 2) beta or CC; 3) gamma or C; 4) delta or CX3C molecules. Each of them recognizes one or more cell surface receptors, named CXCR, CCR, XCR, CX3CR respectively, according to the corresponding subfamily. Many chemokines have been identified within tumor tissues, as a secretory product of tumor cells and/or inflammatory cells. The CXC chemokines (such as IL-8, IP10, Mig, SDF-1 alpha) or CC chemokines (such as MCP-1, MIP-1 alpha, eotaxin, RANTES) have been frequently harvested from tumor tissues or the biological fluids of patients. Some chemokines inhibit tumor growth and progression by activating immunocompetent cytolytic cells or inhibiting tumor-associated angiogenesis. In contrast, other chemokines induce tumor progression by interacting with the specific receptor expressed on the tumor cells and hence by activating chemotaxis and secretion of proteolytic enzymes, or by inducing angiogenesis and metastatic spreading. Sometimes neoplastic cells express chemokine receptors which are not expressed on their normal counterpart. Data from this lab show the CXCR3 expression by cells from lymphoproliferative diseases, such as multiple myeloma and lymphoma, and the stimulation of an invasive phenotype following interaction with specific chemokines.
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PMID:[Chemokines and tumors]. 1248 85

Three mouse strains (BALB/c, ICR, and C3H/He) were injected intratracheally with house dust mites (Der f) four times at 2-week intervals during exposure to diesel exhaust (DE) or clean air for 8 weeks. Der f treatment caused eosinophilic inflammation and proliferation of goblet cells in the airways of the three strains. DE + Der f caused a further increase of eosinophils in BALB/c and ICR mice, but not in C3H/He mice. DE + Der f significantly increased interleukin (IL)-5; regulated on activation, normal T cell expressed, and presumably secreted (RANTES); eotaxin, monocyte chemotactic protein-1 (MCP-1); and macrophage-inflammatory protein-1 alpha (MIP-1 alpha) in all three strains. However, the protein of IL-5 decreased more in C3H/He mice treated with DE + Der f than in mice treated with Air + Der f. The levels of IL-5 in lung tissues corresponded to the pathological changes by Der f and/or DE treatment. The levels of MCP-1 and MIP-1 alpha in the three strains corresponded to the accumulation of lymphocytes in the airway. The adjuvant effect of DE on IgG1 production was observed in the ICR and C3H/He mice. These results suggest that the murine strain differences in the production of eosinophilic airway inflammation by DE + Der f is related to differences in local expression of IL-5, eotaxin, and IgG1 production. The enhancing effects of DE exposure may be mediated mainly by local IL-5.
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PMID:Differences in airway-inflammation development by house dust mite and diesel exhaust inhalation among mouse strains. 1262 82

In order to infect a target cell, the HIV envelope glycoprotein gp 120 has to interact with both the cellular receptor CD4 and an HIV-coreceptor, i.e. the CC or CXC chemokine receptor CCR5 or CXCR4. Both coreceptors were immediately recognized as novel targets for anti-HIV-therapy. Blocking these coreceptors would protect the cell from viral entry and would reduce the viral transmission and pathogenesis. Here we describe the purification and characterization of natural chemokine variants and compare their antiviral activity. In addition, the role of proteases for the processing of the CC chemokines RANTES, eotaxin, MDC and MIP-1 alpha and of the CXC chemokine SDF-1 are studied. The MIP-1 alpha-isoform LD78 beta, that was purified form natural sources, inhibited HIV-infection completely in CCR5-transfected cells, mononuclear leukocytes and purified monocytes at low (ng/ml) concentrations. This research will make it feasible to develop specific chemokine-analogs that block HIV-entry. Deciphering the processes that play a role during the complicated interactions between HIV-gp120 and the cellular membrane may lead to a more efficient treatment of HIV-infections.
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PMID:[Role of chemokines in the HIV infection process]. 1264 32

According to a previous report, the degree of the host immune response highly correlates with severity of the disease in the murine model for neurocysticercosis. In wild-type mice, Mesocestoides corti infection induced a rapid and extensive accumulation of gamma delta T cells and macrophages in the brain. NK cells, dendritic cells, alpha beta T cells, and B cells were also recruited to the brain but at lower levels. In contrast, gamma delta T-cell-deficient mice exhibited decreased cellular infiltration and reduced central nervous system (CNS) pathology. To understand the mechanisms of leukocyte recruitment into the CNS, chemokine expression was analyzed in infected brains in the present study. MCP-1 (CCL2), MIP-1 alpha (CCL3), and MIP-1 beta (CCL4) were up-regulated within 2 days after M. corti infection. Protein expression of RANTES (CCL5), eotaxin (CCL11), and MIP-2 was detected later, at 1 week postinfection. Correlating with the decreased cellular infiltration, delta chain T-cell receptor-deficient (TCR delta(-/-)) mice exhibited substantially reduced levels of most of the chemokines analyzed (with the exception of eotaxin). The results suggest that gamma delta T cells play an important role in the CNS immune response by producing chemokines such as MCP-1 and MIP-1 alpha, enhancing leukocyte trafficking into the brain during murine neurocysticercosis.
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PMID:CC chemokines mediate leukocyte trafficking into the central nervous system during murine neurocysticercosis: role of gamma delta T cells in amplification of the host immune response. 1270 38

Bacillus anthracis lethal toxin (LT) is the major virulence factor of anthrax and reproduces most of the laboratory manifestations of the disease in animals. We studied LT toxicity in BALB/cJ and C57BL/6J mice. BALB/cJ mice became terminally ill earlier and with higher frequency than C57BL/6J mice. Timed histopathological analysis identified bone marrow, spleen, and liver as major affected organs in both mouse strains. LT induced extensive hypoxia. Crisis was due to extensive liver necrosis accompanied by pleural edema. There was no evidence of disseminated intravascular coagulation or renal dysfunction. Instead, analyses revealed hepatic dysfunction, hypoalbuminemia, and vascular/oxygenation insufficiency. Of 50 cytokines analyzed, BALB/cJ mice showed rapid but transitory increases in specific factors including KC, MCP-1/JE, IL-6, MIP-2, G-CSF, GM-CSF, eotaxin, FasL, and IL-1beta. No changes in TNF-alpha occurred. The C57BL/6J mice did not mount a similar cytokine response. These factors were not induced in vitro by LT treatment of toxin-sensitive macrophages. The evidence presented shows that LT kills mice through a TNF-alpha-independent, FasL-independent, noninflammatory mechanism that involves hypoxic tissue injury but does not require macrophage sensitivity to toxin.
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PMID:Bacillus anthracis lethal toxin induces TNF-alpha-independent hypoxia-mediated toxicity in mice. 1295 14

Respiratory syncytial virus (RSV) is a major cause of respiratory tract disease in infants, aged adults, and immunosuppressed patients. The only approved medicines for RSV disease are administration of prophylatic antibodies or treatment with a synthetic nucleoside. Both approaches are expensive and the latter is not without risk and of controversial benefit. The present investigation studied whether pharmaceutical or biologic compounds based upon chemokines might be useful in preventing RSV disease. Of interest was RANTES/CCL5, which inhibits infection by HIV strains that use chemokine receptor (CCR)-5 as co-receptor. Herein, we report that prior or simultaneous treatment of HEp-2 cells with recombinant human CCL5 provides dose-dependent inhibition of infection with RSV. Other recombinant chemokines (MIP-1alpha/CCL3, MIP-1beta/CCL4, MCP-2/CCL8, eotaxin/CCL11, MIP-1delta/CCL15, stromal cell derived factor (SDF)-1alpha/CXCL12) were not inhibitory. The data suggested that CCL5 might inhibit infection by blocking fusion (F) protein-epithelial cell interactions. Infections by mutant RSV strains deleted of small hydrophobic and/or attachment proteins and only expressing F protein in the envelope were inhibited by prior treatment with CCL5 or a biologically inactive N-terminally modified met-CCL5. Inhibition was also observed when virus adsorption and treatment with CCL5 were performed at 4 degrees C. Flow cytometry further revealed that epithelial cells were positive for CCR3, but not CCR1 or CCR5. Thus, novel mimetics of CCL5 may be useful prophylatic agents to prevent respiratory tract disease caused by RSV.
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PMID:Inhibition of respiratory syncytial virus infection with the CC chemokine RANTES (CCL5). 1512 8

Bleomycin yields pulmonary injury characterized by inflammation that proceeds to fibrosis. The production of IL-10 by pulmonary macrophages is increased in the inflammation that accompanies bleomycin lung injury. In the present study, IL-10 deficient and wildtype mice received 0.075 units of bleomycin intratracheally at day 0 and were sacrificed at day 7 or day 14. At day 7, pulmonary inflammation was increased in IL-10-deficient mice as reflected by increased representation of CD3+ and CD4+ lymphocytes and GR-1+ pulmonary granulocytes in the bronchoalveolar lavage (BAL) fluid. Pulmonary interstitial CD80+ and CD86+ mononuclear cells were increased in situ. At day 14, mononuclear cell inflammation was comparable between groups but pulmonary eosinophils were increased in the wildtype. There was no difference in the degree of pulmonary fibrosis, as judged by histology or lung hydroxyproline content. Lung chemokine expression of MIP-1alpha/beta, MIP-2, and eotaxin was increased at days 7 and 14 with a trend towards increased MCP-1 expression at day 14. The findings suggest an immunomodulatory role for IL-10 in the inflammatory response but not in the pulmonary fibrosis yielded by bleomycin.
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PMID:IL-10 inhibits inflammation but does not affect fibrosis in the pulmonary response to bleomycin. 1512 2

Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages (M phi) derived from certain inbred strains. We used nine inbred strains and two inducible nitric oxide synthase (iNOS) knockout C57BL/6J strains polymorphic for the LT M phi sensitivity Kif1C locus to analyze the role of M phi sensitivity (to lysis) in LT-mediated cytokine responses and lethality. LT-mediated induction of cytokines KC, MCP-1/JE, MIP-2, eotaxin, and interleukin-1 beta occurred only in mice having LT-sensitive M phi. However, while iNOS knockout C57BL/6J mice having LT-sensitive M phi were much more susceptible to LT than the knockout mice with LT-resistant M phi, a comparison of susceptibilities to LT in the larger set of inbred mouse strains showed a lack of correlation between M phi sensitivity and animal susceptibility to toxin. For example, C3H/HeJ mice, harboring LT-sensitive M phi and having the associated LT-mediated cytokine response, were more resistant than mice with LT-resistant M phi and no cytokine burst. Toll-like receptor 4 (Tlr4)-deficient, lipopolysaccharide-nonresponsive mice were not more resistant to LT. We also found that CAST/Ei mice are uniquely sensitive to LT and may provide an economical bioassay for toxin-directed therapeutics. The data indicate that while the cytokine response to LT in mice requires M phi lysis and while M phi sensitivity in the C57BL/6J background is sufficient for BALB/cJ-like mortality of that strain, the contribution of M phi sensitivity and cytokine response to animal susceptibility to LT differs among other inbred strains. Thus, LT-mediated lethality in mice is influenced by genetic factors in addition to those controlling M phi lysis and cytokine response and is independent of Tlr4 function.
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PMID:Mouse susceptibility to anthrax lethal toxin is influenced by genetic factors in addition to those controlling macrophage sensitivity. 1527 1

Chemokines regulate the recruitment of leukocytes to sites of inflammation and may therefore play an important role in lymphocyte trafficking between draining lymph nodes and pancreatic islet tissue allografts. The intragraft expression of alpha- and beta-chemokine mRNA during the rejection of BALB/c proislet (fetal precursor islet tissue) allografts in CBA/H mice was assessed quantitatively and semiquantitatively by RT-PCR analyses. Allograft rejection was associated with the strongly enhanced (from day 4) and prolonged expression (up to day 10) of the alpha-chemokine IP-10 and enhanced intragraft mRNA expression of the beta-chemokines MCP-1, MIP-lalpha, MIP-1beta, RANTES, and eotaxin. Peak transcript expression was identified at day 4 (IP-10, MCP-1), day 5 (eotaxin), day 6 (MIP-1alpha, MIP-1beta), and day 14 (RANTES). To examine the role of beta-chemokine receptors in allograft rejection, additional allografts to CCR2-/- , CCR5-/-, and wild-type CCR+/+ mice were analyzed by histology, immunohistochemistry, and morphometry. In CCR5-/- mice, the intragraft recruitment of T cells and macrophages was slower and allograft destruction was delayed; in CCR2-/- mice, the initial entry of macrophages was retarded but graft survival was not prolonged. These findings suggest that IP-10 regulates the initial influx of T cells into proislet allografts, MCP-1/CCR2 signaling controls initial macrophage entry, and the MIP-1alpha, MIP-1beta, and RANTES/CCR5 pathway contributes to the rejection response by subsequently amplifying the recruitment of T cell subpopulations required for graft destruction.
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PMID:The contribution of chemokines and chemokine receptors to the rejection of fetal proislet allografts. 1556 63

Asthma is a serious health problem and during the last decade various experimental models of asthma have been developed to study the pathogenesis of this disease. In this study we describe a new mouse model of asthma that uses the spores of Alternaria alternata and Cladosporium herbarum, two allergenic molds recognized as common inducers of rhinitis and asthma in humans. Here we demonstrate that A. alternata and C. herbarum spores are immunogenic when injected into BALB/c mice, and induce the production of specific IgM and IgG1 antibodies and strongly increase IgE serum levels. To induce the allergic response, mice were sensitized by two intraperitoneal (i.p.) injections and then intranasaly (i.n.) challenged with A. alternata and C. herbarum spores. Bronchoalveolar lavages (BALs) from these mice contained numerous macrophages, neutrophils, eosinophils and lymphocytes whereas neutrophils were the predominant BAL inflammatory cells in nonsensitized mice. Histological studies demonstrated an influx of eosinophils in peri-vascular and peri-bronchial areas and the presence of numerous epithelial goblet cells only in sensitized mice. Increased expression of mRNA specific for various chemokines (eotaxin, MIP-1alpha, MIP-2) and chemokine receptors (CCR-1, CCR-2 and CCR-5) was observed in the lungs of nonsensitized mice challenged with the spores. Expression of CCR-3 mRNA in the lungs and Th2 cytokine (IL-4, IL-5 and IL-13) secretion in the BAL was additionally observed in sensitized and challenged mice. Finally we demonstrate through whole-body plethysmography that mold spore sensitization and challenge induce the development of an airway hyperreactivity in response to nebulized methacholine.
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PMID:A new mouse model of lung allergy induced by the spores of Alternaria alternata and Cladosporium herbarum molds. 1565 16


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