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/intercrines are structurally and functionally related cytokines that induce specific actions on the immune system and are released in response to infection, inflammation, and trauma. These pathological processes are frequently accompanied with food intake suppression. In the present study, the action of chemokines/intercrines on the regulation of feeding was investigated using the intracerebroventricular microinfusion of chemokine/intercrine-alpha subfamily members [interleukin-8 (IL-8); growth-related cytokine/melanoma growth-stimulating activity (GRO-alpha/MGSA); platelet factor-4 (PF-4); beta-thromboglobulin (beta-TG); and interferon-inducible protein-10 (IP-10)] and beta-subfamily members [monocyte chemotactic protein-1/monocyte chemotactic and activating factor (MCP-1/MCAF); regulated upon activation normal T-cell expressed and presumably secreted (RANTES); macrophage inflammatory protein-1 alpha (MIP-1 alpha); and macrophage inflammatory protein-1 beta (MIP-1 beta)]. The doses administered were 1.0, 20, and 100 ng/rat of the chemokine/intercrine. The intracerebroventricular administration of three members of the alpha-subfamily (IL-8, PF-4, and IP-10) and two members of the beta-subfamily (MCP-1/MCAF and RANTES) decreased the short-term (2-h) food intake. These effective chemokines/intercrines, however, were significantly less potent than IL-1 beta in decreasing feeding. The results support the hypothesis that only a subset of immunomodulators released during pathological processes may participate in the regulation of feeding with different potencies.
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PMID:Chemokines/intercrines and central regulation of feeding. 751 92

In the present study we investigated the ability of three monocyte chemokines (MCP-1, MIP-1 alpha, and RANTES) to modulate monocyte adhesion molecules in an attempt to evaluate their potential to induce tissue infiltration of macrophages in vivo. All three chemokines tested induced increased expression of the alpha-chains of two members of beta 2 family of integrins, CD11b and CD11c, and their common beta-chain (CD18). They had no effect on CD11a expression. Enhancement of CD11b and CD11c was dose dependent and followed a distinct time course with peak levels at 4 h. Levels declined to reach basal levels by 24 h. In contrast, IL-1 induced enhancement remained high after 24 h of stimulation. However, the increases caused by chemokines were not mediated by IL-1 as indicated by lack of inhibition by the IL-1R antagonist. Studies on the mechanism of integrin up-regulation showed that mobilization of cytosolic free calcium is an important signaling event in this response and that up-regulation is associated with mobilization from intracellular pools mediated by microtubules. Enhanced CD11b and CD11c expression by chemokines was also found to result in enhancement of monocyte binding to endothelial cells. Further studies indicated that monocyte binding to endothelial cells follows similar dose-response kinetics as the up-regulation of integrins and can be partially blocked by Abs to CD11b and CD11c. These results suggest that modulation of the integrin expression by chemokines may facilitate the tissue trafficking of monocytes during inflammation.
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PMID:Regulation of monocyte integrin expression by beta-family chemokines. 752 13

We have demonstrated the detection of proallergic cytokines in the nasal secretions after antigen challenges. Our aim was to determine the secretion kinetics of chemokines (interleukin [IL]-8, macrophage inflammatory protein-1 alpha [MIP-1 alpha], and RANTES) and other cytokines (IL-1 beta and granulocyte/macrophage colony-stimulating factor [GM-CSF] after allergen challenges and their inhibition by steroid therapy. Ten allergic patients were given either beclomethasone dipropionate (BDP) or placebo in a double-blind, randomized, crossover manner. Allergen challenges were performed after 1 wk of treatment. Nasal secretions were collected serially for 11 h after allergen challenge by a matrix method. Subjects maintained symptom scores at each time point of nasal secretion recovery. Cytokines were measured by specific enzyme-linked immunosorbent assays. The mean peak values for each cytokine and total symptom scores during the early (ER) and/or late-phase reactions (LPR) were significantly reduced during the BDP treatment period (p < 0.05). The levels of cytokine correlated (p < 0.05) with corresponding total symptom scores during ER (IL-1 beta and MIP-1 alpha) and LPR (all cytokines). Our findings document local elevations of IL-1 beta, GM-CSF, and chemokines in the nasal secretions after allergen challenges and their inhibition by steroids. We speculate that the inhibition of cytokine production and secretion in the nasal mucosa may contribute to the clinical efficacy of topical steroids.
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PMID:Secretion of chemokines and other cytokines in allergen-induced nasal responses: inhibition by topical steroid treatment. 754 59

The regulation of CD4 expression on macrophages and its role in immune cell interactions remain obscure. In contrast with primary lymphocytes, primary macrophages express only low amounts of surface CD4, which is regulated differentially for example by adherence in vitro. We report that addition of LPS for 1-5 days to human blood monocyte tissue culture-derived macrophages (TCDM) down-regulates both surface CD4 expression and total cellular CD4 antigen content as measured by flow cytometry and Western blot analysis. TNF-alpha and IL-1 beta, proinflammatory cytokines which are both induced by LPS, also down-regulate surface and total CD4 expression in TCDM. This down-regulation of CD4 expression by LPS, TNF-alpha, and IL-1 beta occurs at the level of transcription. The decreased macrophage CD4 expression induced by LPS was blocked by MoAbs directed against human TNF-alpha and IL-1 beta, demonstrating that LPS acts on CD4 expression through induction of endogenous TNF-alpha and IL-1 beta. Conversely, neither LPS nor TNF-alpha and IL-1 beta were able to modulate surface CD4 expression on quiescent or phytohaemagglutinin (PHA)-activated lymphocytes. Of other cytokines and growth factors tested, Th2 cytokines (IL-4, IL-10, IL-13), chemokines (MCP-1, MIP-1 alpha, RANTES), and macrophage colony-stimulating factor did not alter CD4 expression in primary macrophages; granulocyte-monocyte colony-stimulating factor and the prototypal Th1 cytokine interferon-gamma (IFN-gamma) modulated surface CD4 expression only after prolonged treatment (5 days). Our results show that LPS, TNF-alpha and IL-1 beta selectively down-regulate CD4 expression in primary human macrophages, and that decreased CD4 expression induced by LPS results from endogenous secretion of TNF-alpha and IL-1 beta by the macrophages.
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PMID:Lipopolysaccharide (LPS) down-regulates CD4 expression in primary human macrophages through induction of endogenous tumour necrosis factor (TNF) and IL-1 beta. 758 2

Macrophages, within the cytokine network, are a major source of many cytokines involved in immune response, hematopoiesis, inflammation and many other homeostatic processes. Upon stimulation by micro-organisms, microbial products or endogenous factors including cytokines, macrophages can de novo synthesize and release a large variety of cytokines (ie IL-1, IL-1ra, IL-6, IL-8, IL-10, IL-12, TNF alpha, IFN alpha, IFN gamma, MCP-1, MCP-3, MIF, M-CSF, G-CSF, GM-CSF, MIP-1, MIP-2, LIF, OSM, TGF beta). Some cytokines can upregulate the production of cytokines by macrophages (IL-3, GM-CSF, IFN gamma) while others can inhibit it (IL-4, IL-10, IL-13, TGF beta). In addition, these cytokines can modulate most of the macrophage functions and cell surface marker expression. Other cytokines (the chemokines such as MCP-1,2,3, MIP-1,2 and RANTES) contribute to the recruitment of circulating monocytes within tissues. It is worth noting that macrophages can be their own source of regulatory cytokines.
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PMID:Cytokines and macrophages. 785 54

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

The CC chemokine monocyte chemoattractant protein-3 (MCP-3) activates human monocytes, lymphocytes, basophils, and eosinophils. MCP-3 has been reported to induce [Ca2+]i changes in cells transfected with the monocyte-selective MCP-1 receptor 2B (CC CKR2B) and competes for 125I-MCP-1 binding on CC CKR2B, suggesting that it may mediate monocyte responses to MCP-3. However, we now show that MCP-3 is a ligand and potent agonist for the macrophage inflammatory protein-1 alpha (MIP-1 alpha)/regulated on activation, normal T expressed, and secreted protein (RANTES) receptor CC CKR1 (rank order for [Ca2+]i changes = MIP-1 alpha > MCP-3 > RANTES), which is expressed in monocytes > neutrophils > eosinophils. 125I-MCP-3 bound directly to CC CKR1 and CC CKR2B (Ki = 8 and 7 nM, respectively). Binding to CC CKR1 was competed by all CC chemokines tested except MCP-1. In contrast, binding to CC CKR2B was competed only by MCP-3 and MCP-1. Both MCP-1 and MCP-3 were equipotent agonists (EC50 = 10 nM for [Ca2+]i changes). Thus, MCP-3 is a functional ligand for both CC CKR1 and CC CKR2B, which otherwise have distinct selectivities for CC chemokines. These data suggest that monocyte responses to MCP-3 could be mediated by both CC CKR2B and CC CKR1, whereas eosinophil responses to MCP-3 could be mediated by CC CKR1.
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PMID:Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B. 853 Mar 54

Extension of recombinant human RANTES by a single residue at the amino terminus is sufficient to produce a potent and selective antagonist. RANTES is a proinflammatory cytokine that promotes cell accumulation and activation in chronic inflammatory diseases. When mature RANTES was expressed heterologously in Escherichia coli, the amino-terminal initiating methionine was not removed by the endogenous amino peptidases. This methionylated protein was fully folded but completely inactive in RANTES bioassays of calcium mobilization and chemotaxis of the promonocytic cell line THP-1. However, when assayed as an antagonist of both RANTES and macrophage inflammatory polypeptide-1 alpha (MIP-1 alpha) in these assays, the methionylated RANTES (Met-RANTES) inhibited the actions of both chemokines. T cell chemotaxis was similarly inhibited. The antagonistic effect was selective since Met-RANTES had no effect on interleukin-8- or monocyte chemotractant protein-1-induced responses in these cells. Met-RANTES can compete with both [125I]RANTES and [125I]IMP-1 alpha binding to THP-1 cells or to stably transfected HEK cells recombinantly expressing their common receptor, CC-CKR-1. These data show that the integrity of the amino terminus of RANTES is crucial to receptor binding and cellular activation.
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PMID:Extension of recombinant human RANTES by the retention of the initiating methionine produces a potent antagonist. 857 27

Whether the chemokines macrophage inflammatory protein-1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted (RANTES), which interact specifically with glycosaminoglycans and thus mediate the recruitment, attachment, and migration of leukocytes to vascular endothelia and extracellular matrix, are also involved in interactions between CD4+ murine T lymphocytes and keratinocytes was examined. We have previously observed that depending on the local pH, a mammalian extracellular matrix-degrading enzyme, endo-beta-D glucuronidase (heparanase), which cleaves heparin sulfate proteoglycans, can function wither as an enzyme or as an adhesion molecule for CD4+ T lymphocytes. Herein, the involvement of heparanase in T cell-keratinocyte interactions was also probed. At 37 degree C and pH 7.2, radioactively labeled MIP-1 beta, RANTES, and heparanase bound to confluent layers of resting keratinocytes in a saturable and an heparan sulfate- or heparin-dependent manner, and thereby induced the adhesion of resting CD4+ T cells to keratinocytes. At a relatively acidic pH characteristic of inflammatory milieu, enzymatically active heparanase did not bind to the keratinocytes but, rather, inhibited the binding of MIP-1beta, RANTES, and the enzymatically quiescent heparanase to keratinocytes. These results suggest that certain chemokines and heparanase may function to restrict passing leukocytes, notable T lymphocytes, in the cutaneous micro-environment, a site which is continuously challenged with antigens. These keratinocyte-bound lymphocytes can serve as a reservoir of immediate responders to immunological stimuli.
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PMID:Keratinocytes-associated chemokines and enzymatically quiescent heparanase induce the binding of resting CD4+ T cells. 860 23

We examined the genetic expression of 2 CXC chemokines (IL-8, IP-10), 5 CC chemokines (MCP-1, MIP-lalpha, MIP-1beta, RANTES, 1309) and 1 C chemokine (SCM-1/lymphotactin/ATAC) in various human T-cell lines. By Northern blot analysis, HTLV-1-positive T-cell lines were found to express a number of chemokine genes at variable levels and in different combinations. However, none of the chemokine genes was expressed in HTLV-1-negative T-cell lines. We further confirmed secretion of 3 chemokines (IL-8, MIP-1alpha and RANTES) by some HTLV-1-positive T-cell lines. To examine the role of the HTLV-1-encoded transactivator Tax in the induction of these chemokine genes, we used JPX-9 and JPX-M, which were stably transformed with tax and non-functional tax, respectively, under the control of a metallothionein promoter. Induction of tax in JPX-9 with Cd2+ was accompanied by rapid induction of IL-8, IP-10, MIP-1alpha, MIP-1beta, 1309 and SCM-1 as determined by reverse transcription PCR. No such induction was seen in JPX-M. We thus suggest that Tax is, at least in part, responsible for constitutive expression of certain chemokine genes in HTLV-1-infected T cells. Aberrant production of various chemokines by HTLV-1- infected T cells may impact on the pathophysiology of HTLV-1-associated diseases.
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PMID:Constitutive expression of various chemokine genes in human T-cell lines infected with human T-cell leukemia virus type 1: role of the viral transactivator Tax. 860 55


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