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

We studied the effects of various chemokines including neutrophil-activating peptide 2 (NAP-2), beta-thromboglobulin (beta-TG), platelet factor 4 (PF-4), melanoma growth stimulating activity (GRO), gamma interferon-induced protein (IP-10), regulated on activation, normal T expressed and secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, and monocyte chemotactic protein 1 (MCP-1) on Immunoglobulin (IgE) and IgG4 production by human B cells. None of these chemokines with or without interleukin (IL-4), anti-CD40 or -CD58 monoclonal antibody (mAb), induced IgE and IgG4 production by B cells from nonatopic donors. However, RANTES and MIP-1 alpha selectively enhanced IgE and IgG4 production induced by IL-4 plus anti-CD40 or -CD58 mAb without affecting production of IgM, IgG1, IgG2, IgG3, IgA1, or IgA2, whereas other chemokines failed to do so. Enhancement of IgE and IgG4 production by RANTES and MIP-1 alpha was specifically blocked by anti-RANTES mAb and anti-MIP-1 alpha antibody (Ab), respectively, whereas anti-IL-5 mAb, anti-IL-6 mAb, anti-IL-10 Ab, anti-IL-13 Ab, and anti-tumor necrosis factor-alpha mAb failed to do so. Purified surface IgE positive (slgE4) and slgG4+ B cells generated either in vitro or in vivo spontaneously produced IgE and IgG4, respectively, whereas sIgE- and sIgG4- B cells failed to do so. RANTES and MIP-1 alpha enhanced spontaneous IgE and IgG4 production in slgE+ and slgG4- B cells, respectively, whereas neither RANTES nor MIP-1 alpha did so in sIgE- or sIgG4- B cells. Purified sIgE4+ and sIgG4+, but not sIgE- or sIgG4- B cells, generated in vitro and in vivo expressed receptors for RANTES and MIP-1 alpha, whereas they failed to express receptors for other chemokines. These findings indicate that RANTES and MIP-1 alpha enhance IgE and IgG4 production by directly stimulating sIgE+ and sIgG4+ B cells.
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PMID:RANTES and macrophage inflammatory protein 1 alpha selectively enhance immunoglobulin (IgE) and IgG4 production by human B cells. 864 52

Once infected by obligate intracellular pathogens, monocytes/macrophages release cytokines that activate natural killer (NK) cells. NK cells in turn produce and secrete monocyte/macrophage activating factors such as interferongamma (IFN-gamma), which are important in the early control of these infections. Here we demonstrate that human NK cells are potent producers of another monocyte/macrophage-activating factor, macrophage inflammatory protein-1 alpha (MIP-1 alpha). Fresh NK cells produce negligible amounts of MIP-1 alpha after stimulation with the monocyte-derived cytokines IL-12, TNF-alpha, IL-1 beta, or IL-10, while stimulation with IL-15 alone results in modest MIP-1 alpha production. Abundant NK cell production MIP-1 alpha is seen after costimulation with IL-12 and IL-15, and is dose-dependent. Combinations of IL-12, with TNF-alpha, IL-1 beta, or IL-10 are substantially less effective inducers of MIP-1 alpha production by NK cells. NK cell MIP-1 alpha mRNA transcripts were detectable within 1 h after costimulation with IL-12 plus IL-15 and steadily increased over 24 h, with a concomitant increase in protein production detectable at 12 h. Resting NK cells constitutively express mRNA transcript for a MIP-1 alpha receptor, and costimulation with IL-12 and IL-15 upregulates its level of expression. Equilibrium binding studies with radioiodinated MIP-1 alpha were consistent with the induction of a single class of high affinity MIP-1 alpha receptors on NK cells costimulated with IL-12 and IL-15. Addition of exogenous MIP-1 alpha to resting NK cells did not enhance cytokine production, but did increase NK cytotoxic activity. The requirement for IL-15 as a critical cofactor for NK cell production MIP-1 alpha suggests a potentially unique role for this monocyte-derived cytokine in combination with IL-12. As MIP-1 alpha is known to potentiate the action of IFN-gamma on monocytes and to suppress human immunodeficiency virus replication, the NK cell's production of MIP-1 alpha may be important during the innate immune response to infection.
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PMID:Human natural killer cells produce abundant macrophage inflammatory protein-1 alpha in response to monocyte-derived cytokines. 867 82

Several studies have shown that CC chemokines attract T lymphocytes, and that CD45RO+, memory phenotype cells are considered to be the main responders. The results, however, have often been contradictory and the role of lymphocyte activation and proliferation has remained unclear. Using CD45RO+ blood lymphocytes cultured under different stimulatory conditions, we have now studied chemotaxis as well as chemokine receptor expression. Expression of the RANTES/MIP-1 alpha receptor (CC-CKR1) and the MCP-1 receptor (CC-CKR2) was highly correlated with migration toward RANTES, MCP-1, and other CC chemokines, and was strictly dependent on the presence of IL-2 in the culture medium. Migration and receptor expression were rapidly downregulated when IL-2 was withdrawn, but were fully restored when IL-2 was added again. The effect of IL-2 could be partially mimicked by IL-4, IL-10, or IL-12, but not by IL-13, IFN gamma, IL-1 beta, TNF-alpha, or by exposure to anti-CD3, anti-CD28 or phytohemagglutinin. Activation of fully responsive lymphocytes through the TCR/CD3 complex and CD28 antigen actually had the opposite effect. It rapidly downregulated receptor expression and consequent migration even in the presence of IL-2. In contrast to the effects on CC chemokine receptors, stimulation of CD45RO+ T lymphocytes with IL-2 neither induced the expression of the CXC chemokine receptors, IL8-R1 and IL8-R2, nor chemotaxis to IL-8. The prominent role of IL-2 in CC chemokine responsiveness of lymphocytes suggests that IL-2-mediated expansion is a prerequisite for the recruitment of antigen-activated T cells into sites of immune and inflammatory reactions.
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PMID:Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes. 876 Jul 84

Interleukin 13 (IL-13) is a recently described protein secreted by activated T cells and is a potent in vitro modulator of human monocyte and B-cell functions. IL-13 shares some biologic properties as well as structural similarities with IL-4. Macrophage-inflammatory protein 1 alpha (MIP-1 alpha) is a product of activated monocytes and macrophages and an important activator of T cells, monocytes, and macrophages. We determined the effect of human recombinant IL-13 on lipopolysaccharide (LPS)- and IL-1 beta-induced MIP-1 alpha mRNA and protein expression from peripheral blood monocytes (PBM) and alveolar macrophages (AM). In PBM, basal MIP-1 alpha protein was 20 +/- 7 pM and increased following LPS and IL-1 beta to 1,520 +/- 193 (P < 0.001) and 233 +/- 50 (P < 0.003) pM. IL-13 (25 ng/ml) reduced these values by 55 +/- 10% [not significant (NS)], 43 +/- 9% (P < 0.03), and 44 +/- 15% (NS), respectively. LPS- and IL-1 beta-induced MIP-1 alpha mRNA expression was reduced by 43 +/- 5% (P < 0.01) and 41 +/- 4% (NS). In AM, IL-13 reduced LPS-induced MIP-1 alpha protein release of 2,030 +/- 242 pM by 32 +/- 8% (P < 0.05) and MIP-1 alpha mRNA by 27 +/- 1% (NS). For both PBM and AM, the inhibitory effect of IL-13 on MIP-1 alpha protein was maximal at 24 h, was dose dependent with a maximal effect at 100 ng/ml, and was similar to, although slightly less potent than, that seen with IL-4. In PBM, the inhibitory effect of IL-13 required de novo protein synthesis and was not due to enhanced mRNA decay. Thus, IL-13 has inhibitory effects on the transcription of MIP-1 alpha from monocytes and macrophages, and as is the case with IL-4 and IL-10, may be an important mediator for suppressing inflammatory responses.
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PMID:Interleukin 13 inhibits macrophage inflammatory protein-1 alpha production from human alveolar macrophages and monocytes. 881 Jun 43

Breast feeding improves the health of children. The greatest significance is to host defense, prevention of autoimmunity, and development of the digestive system; however, the underlying mechanisms for these effects are not well understood. Based on recent evidence that cytokines might be important in these processes, we have used ELISA to quantitate the cytokines in human colostrum, transitional, and mature milk from mothers delivering preterm or at term. We also used reverse transcription PCR to test breast milk cells for the production of cytokine mRNA. No significant (< 10 pg/ml) GM-CSF, SCF, LIF, MIP-1 alpha, IL-2, IL-4, IL-11, IL-12, IL-13, IL-15, sIL-2R, or IFN-gamma was detected. And, in contrast to earlier studies using bioassays or RIA, no significant IL-1 beta, TNF-alpha, or IL-6 was present; nor was IL-10, which had been tested using less specific antibodies. We did confirm the presence of high levels of M-CSF, which remained high throughout lactation. Human milk contained latent, but not free, TGF-beta 1, and especially TGF-beta 2, both of which may be activated by gastric acid pH. High levels of IL-1RA were detected, and like activated TGF-beta, may protect against autoimmunity. Chemokines, particularly GRO-alpha and MCP-1, but also RANTES and IL-8, were present and could protect against infection. Maternal cells in breast milk expressed mRNA for MCP-1 (20/20), IL-8 (14/20), TGF-beta 1 (14/16), TGF-beta 2 (4/6), M-CSF (9/12), IL-6 (6/12) and IL-1 beta (7/12), and may be a source of these cytokines. mRNA for IL-2, IL-10, IFN-gamma, TNF-alpha was not detected and only weak expression was found for RANTES (1/18). There was considerable variability between individual women, and women delivering preterm had lower levels of several cytokines in colostrum than women delivering at term. Yet, cytokine levels remained high months to years into lactation, providing immunological benefit to the breastfed infant/child.
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PMID:Cytokines in human milk. 889 39

The roles of complement, proinflammatory cytokines and regulatory cytokines in lung inflammatory injury are becoming defined. Like the proinflammatory cytokines (TNF alpha and IL-1), complement activation products (C5a and/or the membrane attack complex, C5b-9) can directly activate endothelial cells to cause upregulation of adhesion molecules (P-selectin) or can function in a synergistic manner with TNF alpha to cause enhanced upregulation of ICAM-1 and E-selectin. The beta chemokine, MIP-1 alpha, appears to function in vivo as an autocrine activator, enhancing TNF alpha production by pulmonary macrophages, which, in turn, enhances the inflammatory response. Finally, IL-4 and IL-10 have strong regulatory effects by suppressing in vivo production of TNF alpha. There is now compelling evidence to suggest that, in IgG immune-complex-induced lung inflammation in rats, endogenous IL-10 is produced and regulates the intensity of the inflammatory response. Blocking of endogenous IL-10 substantially increases lung TNF alpha production, the recruitment of neutrophils, and the intensity of lung inflammatory injury. Accordingly, the network of cytokines carefully regulates lung inflammatory responses.
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PMID:Role of complement, chemokines, and regulatory cytokines in acute lung injury. 890 17

Allograft rejection is the main cause of corneal graft failure. T lymphocytes and macrophages have been implied to be involved in corneal rejection, but little is known about the molecular mechanism in this process. In this study, cytokine mRNA expression in the cornea was analysed during experimental corneal transplantation. The donor and acceptor corneas of two groups of rats were studied after receiving an allo- (PVG to AO rat) or autograft (AO rat). For controls, central buttons and peripheral corneal rings of the non-transplanted contralateral eyes were used. At different post-operative days (1, 3, 7, 12 and 19), the corneas were removed and subjected to mRNA isolation. All corneal samples underwent semi-quantitative reverse transcriptase-polymerase chain reaction analysis for interleukin-1 beta, interleukin-1, receptor antagonist, interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-alpha, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-2 mRNA expression. Corneal rejection, characterized by opaque corneas with prominent neovascularization, was always diagnosed around day 12. Contralateral, non-grafted corneas showed constitutive mRNA expression for interleukin-1 receptor antagonist and in a few samples also monocyte chemotactic protein-1 and macrophage inflammatory protein-2 mRNA was found. Both allo- and autografts expressed mRNA for the cytokines found in contralateral, non-grafted tissue, as well as for interleukin-1 beta, interleukin-6, interleukin-10 and tumor necrosis factor-alpha. In allografts, the mRNA levels for these cytokines remained constant throughout all post-operative days, with increased interleukin-6 mRNA expression after post-operative day 12. The analysis of the autografts revealed high cytokine mRNA levels until post-operative day 3 or 7, which decreased from then on, except for interleukin-1 receptor antagonist. mRNA for interleukin-2, interleukin-4 and interferon-gamma was not observed in autografts at any time point and in allografts, until post-operative day 12. Interleukin-2 and interferon-gamma mRNA showed maximal expression on POD 12, while in autografts, a marked decrease was observed after POD 3. IL-10 mRNA levels decreased immediately after POD 1 in autografted eyes. For TNF-alpha, an increased mRNA expression starting on POD 7 was found in recipient rings of allografted eyes, while in autografts a weak expression was seen in some samples. MIP-2 transcription increased on PAD 12, while in autografts, its expression was not markedly different from that detected in the contralateral, non-grafted peripheral cornea.
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PMID:Cytokine mRNA expression during experimental corneal allograft rejection. 894 52

An increasing number of proinflammatory peptides, known as chemokines, are constantly being described and characterized. Because of their proven biologic functions in allergy, AIDS and, in general, inflammatory processes, these proteins have recently gained more attention. In this study we report the identification through bioinformatics of two new human chemokines: MIP-3alpha and MIP-3beta. Both of them belong to the beta- or CC chemokine family. Expression studies indicate that MIP-3alpha is predominantly expressed in lymph nodes, appendix, PBL, fetal liver, fetal lung and several cell lines. However, MIP-3beta expression is restricted to lymph nodes, thymus and appendix. Interestingly enough, both chemokines manifested a pattern of expression strongly regulated by IL-10. In contrast with other CC chemokines, MIP-3beta maps to chromosome 9. Here we show the importance of bioinformatics to discover new molecules with possible therapeutic effects and regulatory functions.
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PMID:Identification through bioinformatics of two new macrophage proinflammatory human chemokines: MIP-3alpha and MIP-3beta. 901 39

Cytokines serve to initiate the acute inflammatory response and to integrate nonspecific and specific immunological responses to infections occurring in perioperative patients. Microbial substances induce macrophages to produce pivotal cytokines (TNF-alpha and IL-1 beta). This results in an activation of other cytokine productions including IL-2, IL-3, IL-4, IL-6, chemokines, and IL-10. Also, other host-originated humoral mediators are released from macrophages, neutrophils, platelets, and endothelial cells Various cytokines are also produced by helper-T (Th) cells, and the Th1/Th2 balance is regulated by cytokines and stress hormones. This nonspecific inflammatory response and specific immunological response which are mediated by cytokines are crucial for the host defense against invading pathogens. On the other hand, the blood levels of TNF-alpha, IL-6, IL-8, and MIP-1 alpha were correlated with the severity and mortality in patients with sepsis. Also we found that in patients with inhalation injury the high IL-8 levels in bronchoalveolar lavage fluid on admission predicted the development of respiratory insufficiency. In severe infection, a systemic release of various cytokines is not properly regulated, and the high blood levels of the proinflammatory cytokines cause an autodestructive systemic inflammatory response syndrome (SIRS). This condition is termed "Cytokine Storm" by the author. In cytokine storm, not only proinflamamtory cytokines, but also anti-inflammatory cytokines appear in circulating blood, leading to septic shock, multiple organ dysfunction, and immunosuppression. With further understanding of the roles of cytokines in sepsis, modulation of cytokine responses could be a new modality of the treatment.
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PMID:[Cytokine-mediated biological response to severe infections in surgical patients]. 903 81

We have previously reported that oral administration of hot water extract of Chlorella vulgaris (CVE) enhances resistance to Listeria monocytogenes through augmentation of Listeria-specific cell-mediated immunity in normal mice and mice with murine acquired immunodeficiency syndrome (MAIDS) caused by murine leukemia virus (MuLV) LP-BM5. To elucidate the mechanisms whereby CVE augments the cell-mediated immunity, we examined the expression patterns of mRNA for cytokines in normal and MAIDS mice given CVE orally after L. monocytogenes infection. The expression levels of IL-1 alpha, IL-12, GM-CSF, MIP and TNF alpha genes were significantly augmented in the peritoneal adherent cells by oral administration of CVE for 2 weeks before Listeria infection. The expression levels of gamma IFN and IL-12 mRNA were significantly higher in the spleen after Listeria infection in CVE-treated mice than in normal mice, while the expression of IL-10 mRNA in the spleen was decreased by CVE administration. In MAIDS mice, oral administration of CVE also augmented the expression of gamma IFN and IL-12 mRNA in the spleen after Listeria infection, while it rather reduced the expression of IL-10 mRNA. These results suggest that CVE may preferentially augment THI responses against Listeria via activation of macrophages to produce IL-12 and enhance host defence against Listeria infection both in normal and MAIDS mice.
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PMID:Effect of hot water extract of Chlorella vulgaris on cytokine expression patterns in mice with murine acquired immunodeficiency syndrome after infection with Listeria monocytogenes. 904 41


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