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)

Immunocompetent cells of the epidermis can interact by the elaboration and recognition of cytokines. Although much new information has been reported concerning the cytokines secreted by keratinocytes, little is known about cytokines derived from Langerhans cells (LC). To address this deficiency, we examined cytokine mRNA profiles in different epidermal preparations from BALB/c mice, taking advantage of the sensitive technique of polymerase chain reaction (PCR), after reverse transcription of mRNA. In assays of epidermal sheets separated from dermis by ammonium thiocyanate, mRNA for IL-1 alpha, IL-1 beta, IL-6, IL-7, tumor necrosis factor alpha (TNF alpha), TNF beta, granulocyte macrophage/colony-stimulating factor (GM-CSF), and macrophage inflammatory protein-1 alpha (MIP-1 alpha) were unequivocally present. By contrast, faint bands were detected for IL-4, IL-5, and interferon gamma (IFN gamma), and no PCR signal was detected for IL-2. Importantly, assays of epidermal cells (EC) dissociated with trypsin revealed similar mRNA profiles. To determine the effects of cell isolation, fluorescence-activated cell sorter (FACS)-purified Ia- EC were first analyzed; all of the previously cited cytokine mRNA were present except for IL-1 beta and MIP-1 alpha. EC depleted of LC by a second technique, lysis using anti-Ia monoclonal antibody and complement, revealed similar profiles, with substantially reduced PCR signals for IL-1 beta and MIP-1 alpha. Finally, FACS-purified LC (Ia+ EC) clearly expressed IL-1 beta and MIP-1 alpha mRNA, a finding that was verified by Southern blotting using internal oligo probes. We conclude that these cell-isolation procedures did not produce substantial alterations in basal mRNA profiles and that LC are the principal source of mRNA for IL-1 beta and MIP-1 alpha among unstimulated EC in mice.
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PMID:Langerhans cells are the major source of mRNA for IL-1 beta and MIP-1 alpha among unstimulated mouse epidermal cells. 138 44

Epidermal Langerhans cells (LC) are considered direct yet immature precursors of dendritic cells (DC) in the draining lymph nodes. Although the development of LC into potent immunostimulatory DC occurs in vitro and has been studied in detail, little is known about their profile of cytokine gene expression. By using reverse transcriptase polymerase chain reaction analysis to screen 16 cytokines followed by Northern blotting for selected analysis, we determined the cytokine gene expression profile of murine LC at different time points in culture when T cell stimulatory activity is increasing profoundly. LC regularly expressed macrophage inflammatory proteins, MIP-1 alpha and MIP-2, and interleukin 1 beta (IL-1 beta). Both MIPs were downregulated upon culture and maturation into DC, whereas IL-1 beta was strongly upregulated in culture. MIP-1 alpha and IL-1 beta mRNA were found only in LC, but not in other epidermal cells. Apart from trace amounts of IL-6 in cultured LC, several macrophage and T cell products were not detected. The cytokine expression profile of LC thus appears distinct from typical macrophages. The exact role of the cytokine genes we found transcribed in LC remains to be determined.
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PMID:Cytokine gene expression in murine epidermal cell suspensions: interleukin 1 beta and macrophage inflammatory protein 1 alpha are selectively expressed in Langerhans cells but are differentially regulated in culture. 140 64

Cytokines mediate many host responses to bacterial infections. We determined the inflammatory activities of five cytokines in the central nervous system: TNF-alpha, IL-1 alpha, IL-1 beta, macrophage inflammatory protein 1 (MIP-1), and macrophage inflammatory protein 2 (MIP-2). Using a rabbit model of meningeal inflammation, each cytokine (except IL-1 beta) induced enhanced blood brain barrier permeability, leukocytosis in cerebrospinal fluid, and brain edema. Homologous antibodies to each mediator inhibited leukocytosis and brain edema, and moderately decreased blood brain barrier permeability. In rabbits treated with anti-CD-18 antibody to render neutrophils dysfunctional for adhesion, each cytokine studied lost the ability to cause leukocytosis and brain edema. After intracisternal challenge with pneumococci, antibodies to TNF or IL-1 prevented inflammation, while anti-MIP-1 or anti-MIP-2 caused only a 2-h delay in the onset of inflammation. We suggest these cytokines have multiple inflammatory activities in the central nervous system and contribute to tissue damage during pneumococcal meningitis.
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PMID:The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis. 240 63

One of the major inducible cytokines secreted by mononuclear phagocytes is macrophage inflammatory protein 1 (MIP-1), which consists of two homologous polypeptides, MIP-1 alpha and MIP-1 beta. MIP-1 alpha possesses chemotactic and stimulatory activities for lymphocytes, eosinophils, and monocytes and may play a role in various pulmonary inflammatory conditions. We investigated the expression and release of MIP-1 alpha from human peripheral blood monocytes (PBM) and alveolar macrophages (AM) after stimulation with lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha, and interferon-gamma and the inhibitory effects of corticosteroids. LPS and IL-1 beta only enhanced MIP-1 alpha mRNA and protein in a dose- and time-dependent fashion. Dexamethasone (10(-9) to 10(-4) M) inhibited the basal and induced production and expression of MIP-1 alpha. In PBM, dexamethasone (10(-6) M) reduced LPS- and IL-1 beta-stimulated production of MIP-1 alpha protein by 50 and 63%, respectively, maximally at 24 h, whereas the inhibition of mRNA expression occurred maximally at 4 h. Similar trends were observed for AM. MIP-1 alpha mRNA decay was only slightly decreased in the presence of dexamethasone. Inhibition of LPS-induced MIP-1 alpha mRNA by dexamethasone was attenuated by the protein synthesis inhibitor cycloheximide, indicating the involvement of a protein intermediate. Corticosteroids are a potent inhibitor of IL-1 beta- and LPS-induced expression of MIP-1 alpha through mechanisms involving mainly inhibition of transcription and to a minor degree by reducing mRNA stability. Corticosteroids may be effective anti-inflammatory agents by preventing the expression of chemokines such as MIP-1 alpha.
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PMID:Corticosteroid inhibition of macrophage inflammatory protein-1 alpha in human monocytes and alveolar macrophages. 748 16

The potential for 41.8 degrees C whole body hyperthermia (WBH) to enhance ionizing irradiation and cytotoxic chemotherapy without a commensurate increase in normal tissue toxicity is currently receiving renewed clinical interest. Additionally, WBH may have other biological sequela which may be clinically exploited. In this paper, data are summarized revealing the ability of WBH to induce elevated plasma levels of granulocyte-colony stimulating factor (G-CSF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) within hours of WBH. Data regarding TNF-alpha shows induction in only a proportion of patients. No induction of C-reactive protein (CRP) or the following cytokines was observed: granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-7 (IL-7), interleukin-11 (IL-11), interleukin-12 (IL-12), macrophage-colony stimulating factor (M-CSF), and macrophage inflammatory protein-1 alpha (MIP-1 alpha). Data regarding interleukin-3 (IL-3) and transforming growth factor-beta 1 (TGF-beta 1) were variable and inconclusive. The implications of these results to past and future clinical trials are discussed.
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PMID:Cytokine induction by 41.8 degrees C whole body hyperthermia. 749 63

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

Dendritic cells, the professional antigen-presenting cells (APC) involved in T cell priming, express CD40, a molecule which triggering plays a key role in B cell growth and differentiation as well as monocyte activation. Herein we demonstrate that dendritic Langerhans cells (D-Lc) generated by culturing cord blood CD34+ progenitor cells with granulocyte/macrophage colony-stimulating and tumor necrosis factor alpha (TNF-alpha) express functional CD40 at a density higher than that found on B cells. Culturing D-Lc on CD40-ligand (CD40L) transfected L cells allowed D-Lc survival as 50 +/- 15% of seeded cells were recovered after 4 d while only 5% survived over control L cells. CD40 activation induced important morphological changes with a reduction of cytoplasmic content and a remarkable increase of dendrite development as well as an altered phenotype. In particular, CD40 triggering induced maintenance of high levels of major histocompatibility complex class II antigens and upregulation of accessory molecules such as CD58, CD80 (B7-1) and CD86 (B7-2). CD40 engagement also seems to turn on D-Lc maturation as illustrated by upregulation of CD25, a molecule usually expressed on interdigitating dendritic cells of secondary lymphoid organs. Finally, CD40 activated D-Lc secreted a limited set of cytokines (TNF-alpha, IL-8, and macrophage inflammatory protein 1 alpha [MIP-1 alpha]) whereas a similar activation induced elutriated monocytes to secrete IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, TNF-alpha, and MIP-1 alpha. As D-Lc activated T cells upregulated CD40L, it is likely that CD40 activation of D-Lc observed herein with a fibroblast cell line stably expressing CD40L, mimics physiological interactions between dendritic cells and T cells.
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PMID:Activation of human dendritic cells through CD40 cross-linking. 752 69

Liver and kidney injury following acute or chronic exposure to cadmium is well characterized. While hepatocytes and endothelial cells of the sinusoids are thought to be the primary cellular targets in the liver, ultrastructural changes may vary depending upon the exposure regimen and the time following administration. Since acute and chronic liver disease is often associated with the presence of cytokines, we investigated the role of proinflammatory cytokines in cadmium-induced hepatotoxicity. Supernatants from cultured liver slices obtained from acute or subchronic cadmium-exposed rats and mice were collected and cytokine secretion was examined. In addition, mRNA transcripts for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, MIP-2, IFN-gamma, and ICAM-1 from livers of treated mice were quantitated by reverse transcription-polymerase chain reaction. Modest increases in secretion of TNF-alpha, IL-1 alpha, and IL-6 were observed in response to cadmium which were enhanced in LPS-primed mice. Additionally, cadmium exposure increased IL-1 alpha, IL-1 beta, TNF-alpha, MIP-2, IL-6, and ICAM-1 mRNA transcripts in the liver. Immunohistochemical analysis revealed that TNF-alpha was associated with nonparenchymal cells in livers of cadmium-treated mice. Cadmium exposure produced a marked increase in plasma hepatocellular enzyme levels (i.e., AST, LDH, SDH), acute phase proteins (i.e., serum amyloid A), and foci formation in the liver, while focal inflammation and serum amyloid A (SAA) secretion, but not plasma enzymes, were further increased in cadmium-exposed mice primed with LPS. SAA secretion and focal inflammation were prevented by pretreatment with antibodies to TNF-alpha, indicating that these pathological manifestations are cytokine dependent. These data indicate that TNF-alpha, released from nonparenchymal cells as well as associated cytokines, are responsible for certain manifestations observed with cadmium-induced hepatotoxicity.
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PMID:Role of tumor necrosis factor-alpha in cadmium-induced hepatotoxicity. 753 60

An influx of eosinophils into the lungs occurs in several pulmonary disorders. However, the mechanisms involved remain unknown. Lung epithelial cell release of eosinophil chemotactic factors such as RANTES or macrophage inflammatory protein-1 alpha (MIP-1 alpha) could account for the influx of eosinophils into the lungs. In order to demonstrate the potential role for lung epithelial cells to release RANTES and/or MIP-1 alpha, we investigated the mRNA expression and protein release in cultured A549 cells. Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) induced a time- and dose-dependent increase in RANTES mRNA expression and protein release. In contrast, MIP-alpha protein release was not detectable in these cells. As corticosteroids decrease the influx of eosinophils into the lungs in vivo, we also investigated the capacity of dexamethasone to decrease the TNF alpha-induced RANTES release and mRNA expression; both were decreased in a time- and concentration-dependent manner. Dexamethasone did not affect the TNF alpha-induced RANTES mRNA half-life and did not require protein synthesis to manifest an inhibitory effect. Supernatant from cells stimulated with TNF alpha and IL-1 beta increased eosinophil chemotaxis and this was also inhibited by dexamethasone. These findings suggest a role for RANTES release by lung epithelial cells in the recruitment of eosinophils into the lungs in pulmonary disorders such as interstitial lung diseases, idiopathic pulmonary fibrosis, or asthma and suggest that one beneficial effect of corticosteroids may be inhibition of lung epithelial cell RANTES mRNA expression and protein release.
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PMID:Glucocorticoid inhibition of RANTES expression in human lung epithelial cells. 753 68

The aim of this study was to compare the inhibitory effect of the tetrapeptide AcSDKP, tumor necrosis factor-alpha (TNF-alpha), which contains the sequence of the peptide, transforming growth factor-beta (TGF-beta), and macrophage inflammatory protein-1 alpha (MIP-1 alpha) on sorted CD34+ cells using both proliferation and clonogenic assays. Although a short treatment with any of the molecules decreased the growth of colony-forming unit granulocyte/macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) progenitors (except for TNF-alpha as it is a greater inhibitor for CFU-GM), further experiments using a 6-day liquid culture in the presence of a combination of growth factors (recombinant human interleukin-3 [rhIL-3], IL-6, IL-1 beta, GM colony-stimulating factor [GM-CSF], G-CSF, erythropoeitin [Epo], and stem cell factor [SCF]) allowed us to determine a number of differences between their effects: 1) TGF-beta and TNF-alpha induced a stronger decrease in the proliferation and clonogenicity of CD34+ subsets than MIP-1 alpha and AcSDKP, 2) the dose-response curves appeared different, and 3) contrary to TGF-beta and TNF-alpha, AcSDKP and MIP-1 alpha required repeated addition to induce inhibition. Therefore, our data clearly show that while the inhibitory effect of TNF-alpha and AcSDKP appeared to be different, there is a close similarity in the effect of AcSDKP and MIP-1 alpha on normal human progenitor response to the combination of growth factors used.
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PMID:Comparison of the inhibitory effect of AcSDKP, TNF-alpha, TGF-beta, and MIP-1 alpha on marrow-purified CD34+ progenitors. 753 83


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