Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of 3'-azido-3'-deoxythymidine (AZT) to patients with acquired immunodeficiency syndrome (AIDS) causes significant anemia and neutropenia. The bone marrow cytotoxicity of AZT has been attributed to deoxyribonucleotide pool perturbations that might result in impaired DNA synthesis in normal bone marrow elements. We examined the effect of human recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on AZT-mediated biochemical perturbations and in vitro growth inhibition of normal bone marrow myeloid progenitor cells. Exposure of nonadherent, bone marrow mononuclear cells (BMMC) to 100 ng/ml of rGM-CSF for 6 h resulted in approximately twofold increments in the mean intracellular deoxycytidine triphosphate (dCTP) and thymidine triphosphate (dTTP) levels. Administration of 10 microM AZT alone to BMMC for 6 h markedly reduced dCTP and dTTP levels and generated significant levels of AZT triphosphate (AZT-TP). Coadministration of rGM-CSF (100 ng/ml) along with AZT (10 microM) partly restored dCTP and dTTP levels and significantly reduced AZT-TP levels. Furthermore, simultaneous exposure of BMMC for 4 h to 100 ng/ml of rGM-CSF reduced the mean DNA incorporation of [3H]AZT (10 microM) from 27.2 to 19.1 pmol/micrograms of DNA. Additionally, the inhibitory effects of AZT (10 microM) on granulocyte-macrophage colony-forming unit (CFU-GM) colony growth were significantly reduced in the presence of 100 ng/ml of rGM-CSF. These in vitro studies suggest that rGM-CSF partly corrects AZT-mediated biochemical perturbations as well as reduces the cytotoxicity of AZT in normal human bone marrow myeloid progenitor cells.
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PMID:The effect of recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) on 3'-azido-3'-deoxythymidine (AZT)-mediated biochemical and cytotoxic effects on normal human myeloid progenitor cells. 278 47

Tristetraprolin (TTP/zinc finger protein 36) family proteins have antiinflammatory effects by destabilizing proinflammatory mRNA. TTP expression is reduced in fats of obese people with metabolic syndrome and brains of suicide victims and is induced by insulin and cinnamon polyphenol extract (CPE) in adipocytes, by lipopolysaccharide (LPS) in macrophages, and by green tea polyphenol extract in rats. CPE was reported to improve immune function against microorganisms, but the mechanism is unknown. This study tested the hypothesis that CPE regulates immune function involving genes encoding TTP, proinflammatory cytokines, and glucose transporter (GLUT) families and compared the effects of CPE to those of insulin and LPS in mouse RAW264.7 macrophages. CPE increased TTP mRNA and protein levels, but its effects were less than LPS. CPE (100 mg/L, 0.5-4 h) increased TTP and tumor necrosis factor (TNF) mRNA levels by up to 2- and 6-fold that of the control, respectively, and the base level of TTP was 6-fold that of TNF. LPS (0.1 mg/L, 4 h) increased TTP, TNF, granulocyte-macrophage colony-stimulating factor, cyclooxgenase-2, and interleukin 6 mRNA levels by 39-1868 fold. CPE and LPS increased GLUT1 expression (the major GLUT form in macrophages) to 3- and 2-fold that of the control, respectively. Insulin (100 nmol/L, 0.5-4 h) did not exhibit major effects on the expression of these genes. CPE increased TTP expression more rapidly than those of proinflammatory cytokines and the net increases of TTP mRNA levels were larger than those of proinflammatory cytokines. These results suggest that CPE can affect immune responses by regulating anti- and proinflammatory and GLUT gene expression.
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PMID:Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages. 1842 88