Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infections, trauma and inflammatory processes induce a host response with increases in a large group of structurally and functionally diverse plasma proteins. Parental administration of foreign proteins also induce an increase in plasma fibrinogen. Interleukin-6 (IL-6) is a monocyte-derived mediator and has regulatory effects on acute phase protein genes which result in the induction of fibrinogen synthesis in primary hepatocytes, while the addition of interleukin-1 (IL-1) exerts a negative modulating influence on the IL-6-stimulated fibrinogen. In order to understand the mechanisms by which IL-1 inhibits IL-6-stimulated fibrinogen transcription and translation, and since IL-1 is believed to act through PGE2 stimulation, we have studied the influence of PGE2 in IL-6 or IL-1, alone and in combination, on Fg mRNA expression (by Northern blot analysis) and the influence of PGE2, indomethacin, and arachidonic acid on Fg secretion. Moreover, since human recombinant interleukin-1 receptor antagonist (hrIL-1ra) is a strong inhibitor of IL-1 induced IL-1 transcription and translation and has an inhibitory effect on PGE2, we have studied the effects of IL-1ra on the down-regulation of IL-6 stimulated fibrinogen by IL-1, using an Fg ELISA method.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1995 Jan 26
PMID:The down-regulation of IL-6-stimulated fibrinogen steady state mRNA and protein levels by human recombinant IL-1 is not PGE2-dependent: effects of IL-1 receptor antagonist (IL-1RA). 777 69

IL-1ra has recently been shown to suppress both cytokine- and endotoxin-induced IL-1 beta and TNF-alpha release from monocytes. Given that mononuclear phagocytes can produce both the proinflammatory cytokines IL-1 alpha, IL-1 beta, and TNF-alpha as well as the suppressive cytokine IL-1ra, we proposed that IL-1 alpha, IL-1 beta, and TNF-alpha may induce IL-1ra from mononuclear phagocytes. To test this hypothesis, human mononuclear cells were stimulated for 18 h with IL-1 alpha, IL-1 beta, or TNF-alpha, and the supernatants assayed for IL-1ra by ELISA. Each cytokine induced IL-1ra secretion in a dose-response manner. However, IL-1 alpha and IL-1 beta were better inducers of IL-1ra than was TNF-alpha. IL-1 alpha or IL-1 beta at a dose of 10 ng/ml induced 3 to 6 ng/ml of IL-1ra, while TNF-alpha at a dose of 100 ng/ml stimulated only 1.4 ng/ml of IL-1ra. This induction was not due to endotoxin, as all cytokines contained less than 10 pg/ml of contaminating LPS. Furthermore, for IL-1 beta-induced IL-1ra, immunoprecipitation of IL-1 beta with an anti-IL-1 beta antibody, but not a preimmune antibody, blocked the induction of IL-1ra. In contrast to mononuclear phagocytes, IL-1 alpha, IL-1 beta, and TNF-alpha did not induce further IL-1ra production in alveolar macrophages. This lack of macrophage responsiveness may relate to the constitutive production of IL-1ra by these mature mononuclear phagocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 May
PMID:Cytokine-induced interleukin-1 receptor antagonist release in mononuclear phagocytes. 817 14

Human alveolar macrophages (AM) are antigen-presenting cells that have an important immune effector function in the lung. We have previously shown that AM produce a specific interleukin-1 (IL-1) inhibitor of 20 to 25 kD that blocks biologic activities of IL-1 alpha and IL-1 beta such as prostaglandin E2 production by fibroblasts. This inhibitor acts as a receptor antagonist (IL-1ra) by binding to the IL-1 receptor. We are now presenting evidence that the natural AM-derived IL-1ra is immunologically identical to IL-1ra cloned from human peripheral blood monocytes and shows a band at 20 kD compatible with the natural glycosylated IL-1ra. No constitutive expression of IL-1 mRNA was detected when analyzed by Northern blot immediately after bronchoalveolar lavage from six control patients. Comparison of in vitro kinetics of IL-1ra, IL-1 alpha, and IL-1 beta analyzed during culture in the presence or absence of phorbol myristate acetate revealed that their mRNA expression was asynchronous. IL-1 alpha and IL-1 beta mRNA were expressed after as little as 15 min, whereas IL-1ra mRNA was detectable only after 3 h in culture. The production of IL-1ra was measured by enzyme-linked immunosorbent assay and compared with that of IL-1 alpha and IL-1 beta. In freshly isolated AM (10(6)/ml), cell-associated IL-1ra was present in an average amount of 2.0 +/- 0.5 ng/ml, i.e., 25 and 100 times more than IL-1 alpha and IL-1 beta, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Feb
PMID:Regulation of interleukin-1ra, interleukin-1 alpha, and interleukin-1 beta production by human alveolar macrophages with phorbol myristate acetate, lipopolysaccharide, and interleukin-4. 842 7

To assess the possible influence of endogenous glucocorticoids on cytokine expression in the brain, adrenalectomized mice and sham operated mice were injected with saline or lipopolysaccharide (LPS, 10 micrograms/mouse, subcutaneously) and the levels of transcripts for IL-1 alpha, IL-1 beta, IL-1ra, IL-6 and tumor necrosis factor-alpha (TNF alpha) were determined 2 h after treatment in the spleen, pituitary, hypothalamus, hippocampus and striatum, using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Levels of IL-1 beta were measured by ELISA in plasma and tissues of mice sacrificed after the administration of LPS or saline. LPS induced the expression of pro-inflammatory cytokines at the mRNA level in all tissues under investigation, except for TNF alpha in the hippocampus. This effect was potentiated by adrenalectomy in the spleen for IL-1 alpha and IL-1ra, the pituitary for cytokines other than IL-1ra, the hypothalamus for all cytokines, the hippocampus for cytokines other than TNF alpha, and the striatum for IL-1 alpha and IL-6. In saline-treated mice, adrenalectomy increased IL-1 alpha and IL-1 beta gene expression in the hypothalamus and IL-1 alpha gene expression in the hippocampus and striatum. LPS increased plasma and tissue levels of IL-1 beta, as determined by ELISA, and this effect was potentiated by adrenalectomy in plasma and tissues other than the spleen. These results can be interpreted to suggest that endogenous glucocorticoids regulate the neural components of the host response to infection and inflammation by inhibiting cytokine expression in peripheral organs and the brain.
Brain Res Mol Brain Res 1996 Feb
PMID:Adrenalectomy enhances pro-inflammatory cytokines gene expression, in the spleen, pituitary and brain of mice in response to lipopolysaccharide. 901 65

The systemic inflammatory response syndrome (SIRS) is characterized by endothelial cell activation causing a generalized inflammatory response and cytokine-mediated pathophysiological alterations. The pathophysiology of SIRS involves changes in the functioning of several endocrine glands, including the pituitary. SIRS-induced alterations in pituitary function include activation of the hypothalamic-pituitary adrenal (HPA) axis causing hypercortisolemia, the euthyroid sick syndrome, and cessation of reproductive function. These changes are in part mediated by cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1). IL-1 function depends on the local ratio of bioactive IL-1 and IL-1 receptor antagonist. Here we review our studies on IL-1 beta and IL-1ra mRNA levels in the pituitary in a rat model of SIRS. We have found that IL-1 beta mRNA peaked at 2 h after lipopolysaccharide (LPS) administration, increasing twelvefold over control values in the posterior pituitary and fivefold over controls in the anterior pituitary. IL-1ra mRNA levels peaked at 6 h post-LPS administration, later than those of IL-1 beta mRNA. IL-1ra mRNA levels increased tenfold in the anterior pituitary, but were induced only threefold in the posterior pituitary. IL-1ra gene expression is profoundly induced in the pituitary in vivo during systemic inflammation and its induction follows that of IL-1 beta, but it is differentially regulated and tissue-specific, occurring predominantly in the anterior pituitary. Future studies of the effects of IL-1 in the pituitary should take into account the local levels of IL-1ra.
Mol Psychiatry 1997 Mar
PMID:Interleukin 1 receptor antagonist gene expression in rat pituitary in the systemic inflammatory response syndrome: pathophysiological implications. 910 26

Plasma levels of antiinflammatory compounds (which counteract inflammation, cortisol, IL-1 receptor antagonist, IL-1ra; soluble IL-2 receptor, sIL-2r, soluble intercellular adhesion molecule-1, sICAM-1; interleukin-10, IL-10) were synchronously determined in a consecutive series of 25 patients with severe bacterial infections. Serum levels of cortisol, IL-1ra, sIL-2r, sICAM-1 and IL-10 were significantly higher in patients with infection compared with healthy volunteers. Bacterial infection results in the production of inflammatory and proinflammatory cytokines from macrophage/monocyte, which are thought to be involved in the pathogenesis of systemic inflammatory response syndrome (SIRS). We found that counter-inflammatory compounds can also be released during infectious insults. These results suggested that the biological activity of inflammatory mediators is inhibited by natural antiinflammatory compounds, and the body itself might down-regulate excessive inflammatory cascades through counteracting the inflammatory responses and restore homeostasis.
Res Commun Mol Pathol Pharmacol 1997 Apr
PMID:Clinical value of cytokine antagonists in infectious complications. 917 65

Alleles of the IL-1 genes are associated with several autoimmune and inflammatory diseases, where they tend to have a role in the severity of the disease rather than in susceptibility to the disease itself. Allele 2 of the variable number tandem repeat (VNTR) polymorphism in the IL-1 receptor antagonist (IL-1ra) gene was the first marker of the IL-1 cluster to be associated in this way with severity of chronic, systemic and local inflammatory diseases. Because of the role that IL-1 also plays in the pathobiology of certain hematopoietic disorders, we aimed at examining the allelic distribution of the IL-1ra VNTR in leukemias, lymphomas and related malignancies. While in patients with chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), multiple myeloma (MM) and related disorders, primary acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and Hodgkin's disease (HD), the allelic distribution of IL-1RN was comparable to that seen in healthy control subjects, in a small group of patients with secondary AML the frequency of the IL-1RN*4 allele appeared to be significantly increased.
Cytokines Mol Ther 1996 Dec
PMID:Polymorphism within the second intron of the IL-1 receptor antagonist gene in patients with hematopoietic malignancies. 938 10

In an earlier study, we showed that a recombinant adenovirus vector with deletions in the E1 and E3 regions of the viral genome (AV1LacZ4) induces expression of interleukin (IL)-8 in A549 cells (a human respiratory cell line). IL-8 can be induced through several pathways, including activation by IL-1. We tested the hypothesis that the induction of IL-8 by the AV1LacZ4 adenovirus is accomplished by means of the IL-1/IL-8 activation pathway, which could be blocked by IL-1 receptor antagonist (IRAP). Viral infections of A549 cells were performed at a multiplicity of infection (MOI) of 50 in the presence and absence of IRAP (50 ng/ml). A549 cells were also stimulated with tumor necrosis factor (TNF)-alpha (100 ng/ml), a known stimulant of IL-8, in the presence and absence of IRAP. IL-8 expression was evaluated by Northern blot analysis and enzyme-linked immunosorbent assay. Levels of IL-8 protein and messenger RNA (mRNA) were greater in the infected cells than in the uninfected ones at 24, 48, and 96 h (P < 0.01). Virus-infected cells treated with IRAP expressed 75% less IL-8 mRNA and protein (P < 0.01) than did untreated cells, whereas IRAP pretreatment of TNF-alpha-stimulated cells did not affect IL-8 production. IL-1 production by the virus-infected cells was detectable by concentration of the supernatants and reverse transcription-polymerase chain reaction. We conclude that IL-8 is produced by virus vector-infected cells, partly through IL-1 activation that can be downregulated by IRAP.
Am J Respir Cell Mol Biol 1999 Sep
PMID:Interleukin-1 receptor antagonist inhibits interleukin-8 expression in A549 respiratory epithelial cells infected in vitro with a replication-deficient recombinant adenovirus vector. 1046 Jul 56

Net blotch, which is caused by the fungus Pyrenophoral teres Drechs. f. teres Smedeg., presents a serious problem for barley production worldwide, and the identification and deployment of sources of resistance to it are key objectives for many breeders. Here, we report the identification of a major resistance gene, accounting for 65% of the response variation, in a cross between the resistant line C19819 and the susceptible cv. Rolfi. The resistance gene was mapped to chromosome 6H with the aid of two recently developed systems of retrotransposon-based molecular markers, REMAP and IRAP. A total of 239 BARE-1 and Sukkula retrotransposon markers were mapped in the cross, and the 30-cM segment containing the locus with significant resistance effect contained 26 of the markers. The type and local density of the markers should facilitate future map-based cloning of the resistance gene as well as manipulation of the resistance through backcross breeding.
Mol Gen Genet 2000 Oct
PMID:Application of BARE-1 retrotransposon markers to the mapping of a major resistance gene for net blotch in barley. 1108 73

Insulin treatment of fat cells results in the translocation of the insulin-responsive glucose transporter type 4, GLUT4, from intracellular compartments to the plasma membrane. However, the precise nature of these intracellular GLUT4-carrying compartments is debated. To resolve the nature of these compartments, we have performed an extensive morphological analysis of GLUT4-containing compartments, using a novel immunocytochemical technique enabling high labeling efficiency and 3-D resolution of cytoplasmic rims isolated from rat epididymal adipocytes. In basal cells, GLUT4 was localized to three morphologically distinct intracellular structures: small vesicles, tubules, and vacuoles. In response to insulin the increase of GLUT4 at the cell surface was compensated by a decrease in small vesicles, whereas the amount in tubules and vacuoles was unchanged. Under basal conditions, many small GLUT4 positive vesicles also contained IRAP (88%) and the v-SNARE, VAMP2 (57%) but not markers of sorting endosomes (EEA1), late endosomes, or lysosomes (lgp120). A largely distinct population of GLUT4 vesicles (56%) contained the cation-dependent mannose 6-phosphate receptor (CD-MPR), a marker protein that shuttles between endosomes and the trans-Golgi network (TGN). In response to insulin, GLUT4 was recruited both from VAMP2 and CD-MPR positive vesicles. However, while the concentration of GLUT4 in the remaining VAMP2-positive vesicles was unchanged, the concentration of GLUT4 in CD-MPR-positive vesicles decreased. Taken together, we provide morphological evidence indicating that, in response to insulin, GLUT4 is recruited to the plasma membrane by fusion of preexisting VAMP2-carrying vesicles as well as by sorting from the dynamic endosomal-TGN system.
Mol Biol Cell 2000 Dec
PMID:Insulin recruits GLUT4 from specialized VAMP2-carrying vesicles as well as from the dynamic endosomal/trans-Golgi network in rat adipocytes. 1110 9


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