Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematopoietic stem cells are capable of self-replication and differentiation to lineage-committed progenitor cells. The progenitors proliferate and differentiate to lineage-specific, morphologically recognizable precursors and, finally, to terminal circulating blood cells. These homeostatic mechanisms are regulated by a complex set of interacting growth stimulatory and inhibitory factors that are produced by, or in collaboration with, the tissue's regulatory microenvironment. A number of well-characterized cytokines have been implicated in the negative regulation of hematopoiesis: ferritin H-subunit (HF), lactoferrin (Lf), prostaglandin E (PGE), tumor necrosis factor (TNF), interferon (IFN), transforming growth factor-beta (TGF beta), acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) or thymosin-beta 4, pyroGlu-Glu-Asp-Cys-Lys (pEEDCK), macrophage inflammatory protein-1 alpha (MIP-1 alpha), inhibin, superoxide dismutase (SOD), glutathione (GSH) and others not well-known yet. The role of inhibitors in restraining stem cells from entering the cell cycle and protecting them from the toxic side effects of chemotherapeutic drugs is opening an alternate strategy for the treatment of cancer patients.
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PMID:[Biomolecules suppressing myelopoiesis]. 134 39

Stimulation of the immune system results in a series of metabolic changes that are antagonistic toward growth. Monokines, including interleukin-1, tumor necrosis factor, and interleukin-6, are released from cells of the monocyte-macrophage lineage after recognition of immunogens. They appear to mediate homeorhetic response, which alters the partitioning of dietary nutrients away from growth and skeletal muscle accretion in favor of metabolic processes which support the immune response and disease resistance. These alterations include 1) decreased skeletal muscle accretion due to increased rates of protein degradation and decreased protein synthesis; 2) increased basal metabolic rate resulting in increased energy utilization; 3) use of dietary amino acids for gluconeogenesis and as an energy source instead of for muscle protein accretion; 4) synthesis by the liver of acute phase proteins; 5) redistribution of iron, zinc, and copper within the body due to the hepatic synthesis of metallothionein, ferritin, and ceruloplasmin; (6) impaired accretion of cartilage and bone; and 7) release of hormones such as insulin, glucagon, and corticosterone. These monokines also influence the differentiation of cells. Tumor necrosis factor suppresses the differentiation of myoblasts and adipocytes whereas the chicken monokine myelomonocytic growth factor induces the differentiation of granulocytes.
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PMID:Monokines in growth and development. 171 68

To clarify the correlation of cytokine level with the severity and prognosis of children with the hemophagocytic syndrome, we analyzed serum interleukin-1 (IL-1) and tumor necrosis factor (TNF) levels in 26 children with either the virus-associated hemophagocytic syndrome (VAHS, n = 12) or malignant histiocytosis (MH, n = 14). When compared to healthy controls, 13 children had an elevated IL-1 (greater than or equal to 20 pg/ml) and 21 children had an elevated TNF (greater than or equal to 10 pg/ml) level at diagnosis. There was however, no significant difference in the frequency of these high levels between the patients with VAHS and MH. Neither IL-1 nor TNF levels correlated with other clinical or laboratory findings in either VAHS or MH. Two of the 12 patients with VAHS died of an intracranial hemorrhage and 7 of the 14 patients with MH died despite chemotherapy. The MH patients who had a high TNF level (greater than or equal to 50 pg/ml) had a poorer prognosis than those with a low TNF level (less than 50 pg/ml; p less than 0.01). In MH patients, other parameters, such as coagulopathy and lactic dehydrogenase, ferritin and IL-1 levels, did not correlate with prognosis. In 3 patients (2 with VAHS and 1 with MH) analyzed periodically, the change in TNF level was closely associated with the clinical progression or regression of the diseases. Serum cytokine levels may thus be monitored not only for predicting the severity and prognosis of VAHS or MH but also for determining the indications for or timing of chemotherapy. Moreover, TNF may play an important role in the progression of VAHS and MH.
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PMID:Prognosis of children with virus-associated hemophagocytic syndrome and malignant histiocytosis: correlation with levels of serum interleukin-1 and tumor necrosis factor. 185 Sep 44

The expression of a major cellular substrate for protein kinase C, the MARCKS protein, is regulated in a cell-, tissue-, and developmental stage-specific fashion; in addition, this expression can be stimulated acutely by various cytokines in certain cell types. We have begun to characterize the human gene in order to elucidate the genetic elements responsible for this highly regulated expression. We first cloned a human MARCKS cDNA, which encoded a predicted protein of 332 amino acids (Mr 31,600) that was approximately 89, 74, and 59% identical to the bovine, mouse, and chicken proteins, respectively. Regions conserved at the amino acid level included the amino-terminal myristoylation consensus sequence, the site of intron splicing, and the phosphorylation site domain. The human cDNA was used to demonstrate that tumor necrosis factor-alpha could rapidly stimulate MARCKS gene transcription in the human promyelocytic leukemia cell line HL60. Genomic clones were then isolated; sequence analysis identified a putative promoter region that had no TATA box and contained multiple transcription initiation sites in a region spanning 57 base pairs (bp). This was followed by a 5'-untranslated region of approximately 400 bp, which displayed a complex predicted secondary structure with a delta G of -73.4 kcal/mol. Plasmid constructions containing between 52 and 1453 bp of the human MARCKS promoter linked to the human growth hormone gene were then used in transient expression experiments. Constructions containing 52 and 110 bp of the MARCKS promoter did not exhibit promoter function while the larger constructions all exhibited promotor function; the 248-bp fragment of the MARCKS promoter was 80% as effective as the human ferritin promoter in stimulating expression of human growth hormone in intact cells. Using an insert from the human genomic clone as a probe, we identified human chromosome 6, q21-qter, as the location of the MARCKS gene; this has been assigned the gene symbol MACS.
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PMID:The human myristoylated alanine-rich C kinase substrate (MARCKS) gene (MACS). Analysis of its gene product, promoter, and chromosomal localization. 186 Aug 46

We have studied transferrin receptor expression in MRC5 human fibroblasts in response to tumor necrosis factor-alpha (TNF, cachectin) or interleukin 1-alpha (IL-1). Treatment of exponentially growing MRC5 cells with these cytokines led to a 3-4-fold increase in transferrin receptor mRNA and a coordinate increase in transferrin receptor protein by 24 h. Under these conditions, stimulation of [3H]thymidine incorporation was minimal, suggesting that the induction of transferrin receptor by TNF and IL-1 is mediated by a growth-independent regulatory mechanism. A study of the time course of this response showed that cytokine-mediated increases in transferrin receptor mRNA and protein proceeded after a lag of 12-24 h. A simultaneous analysis of the effects of TNF and IL-1 on ferritin in MRC5 cells was also performed. Ferritin L mRNA levels were unchanged. However, induction of ferritin H mRNA was seen within 4 h, preceding the induction of the transferrin receptor. The synthesis of ferritin H (but not ferritin L) protein peaked at 8 h after TNF or IL-1 treatment, followed by a rapid decrease in both ferritin H and L protein synthesis. As ferritin H synthesis declined, levels of transferrin receptor protein increased, reaching a maximum by 24 h. These results suggest that the cytokine-dependent induction of ferritin H and subsequent increase in the transferrin receptor are related and possibly interdependent events. This study demonstrates that the complex role of TNF and IL-1 in iron homeostasis includes modulation of the transferrin receptor.
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PMID:Tumor necrosis factor-alpha and interleukin 1-alpha regulate transferrin receptor in human diploid fibroblasts. Relationship to the induction of ferritin heavy chain. 201 26

At present, no sufficient therapy for metastatic renal cell carcinoma is available. Several immunotherapeutical protocols have been studied, success rates, however, were inconsistent. The purpose of this study was to assess the pretherapeutic immunological status of 13 patients with metastatic and 16 patients with nonmetastatic renal cell carcinoma and of 15 healthy volunteers. Determined were differential blood counts, lymphocyte subpopulations, beta 2-microglobulin, tumor necrosis factor (TNF), neopterin, immunoglobulin, fibronectin and ferritin. Additionally, these parameters were recorded for monitoring an immunotherapeutical approach with the xenogeneic biological response modifier Keyhole limpet hemocyanine (KLH) in 10 patients with metastatic and in 5 patients with nonmetastatic disease. The pretherapeutic immunological status of patients with metastatic disease was characterized by significantly reduced T4-, T8- and B-cell counts. Significantly increased were granulocyte counts, beta 2-microglobulin, neopterin and TNF. In patients who did not suffer from metastases, only beta 2-microglobulin and neopterin were increased significantly. During immunotherapy, in patients with metastases, there was a decline of lymphocyte subsets and of the T4/T8-ratio, which correlated with progress of the disease. Humoral immune parameters showed no changes compared to pretherapeutic values. In patients who did not suffer from metastases, cellular immune parameters showed stable values during immunotherapy; neopterin, beta 2-microglobulin and TNF increased considerably. These findings indicate immunosuppression in patients with metastatic renal cell carcinoma, increasing with progression of the disease and possibly impairing the immunostimulating effects of biological response modifiers during immunotherapy. In conclusion, the clinical response of metastatic renal cell carcinoma to immunotherapy might be improved if the immunostimulant is combined with agents suitable to overcome immunosuppression, i.e. low doses of cyclophosphamide or inhibitors of prostaglandin synthesis. In addition, assessment of immune parameters for monitoring the actual immune status of a patient and the immunological effects of therapy was found to be a necessary part of immunotherapy.
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PMID:Immune status and immune therapy of renal cell carcinoma. 221 64

We have investigated the effect of cytokines, including interleukin-6 (Il-6), interleukin-1 alpha (Il-1 alpha), and tumor necrosis factor-alpha (TNF-alpha), on the inducible expression of cytochrome P450s (CYP) CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. The ability of these cultures to mimic the acute phase response when stimulated with cytokines was evaluated using immunoblotting to measure the production of albumin, ferritin, fibrinogen, and ceruloplasmin. The cytokines exhibited specific patterns of action on the production of these proteins. Albumin was depressed by all the cytokines. In contrast to Il-6 and Il-1 alpha, TNF-alpha reduced the production of fibrinogen and ceruloplasmin but stimulated the production of ferritin. When cells were treated with the CYP inducer alone, large increases in the expression of CYP1A1 and CYP1A2 by beta-naphthoflavone and of CYP3A4 by rifampicin were observed at messenger RNA (mRNA) and protein levels, by ribonuclease protection and immunoblotting, respectively. When the cells were treated with the inducer plus cytokines, the induction of mRNA was greatly reduced. Again, specific patterns of action were revealed: Il-6 had the most potent effect on CYP3A4, whereas TNF-alpha was the most potent with CYP1A genes. In all cases, changes at the protein levels paralleled changes at the mRNA levels. In cells preinduced with beta-naphthoflavone or rifampicin, the decay with time of the levels of the CYP1A2 or CYP3A4 proteins, after the removal of the inducer, was not affected by cytokines. We conclude that cytokines strongly repress the inducibility of CYP1As and CYP3A4 genes at a transcriptional or a posttranscriptional level, but affect neither the rate of translation of CYP mRNAs nor the rate of degradation of the CYP proteins in these cultures.
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PMID:Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. 755 64

Iron deficiency is common in hemodialysis patients, particularly if they are on recombinant human erythropoietin (rHuEPO) therapy. Ten anemic patients (hemoglobin concentration 89 +/- 2.2 g/l, mean +/- SEM) on hemodialysis with either storage (serum-ferritin < 60 mg/l) and/or functional (S-transferrin saturation < or = 17%) iron deficiency were followed for 5 weeks. During the first 3 weeks they were given 100 mg of iron dextran on 10 consecutive dialysis sessions. Half of the patients were concomitantly treated with rHuEPO. Iron therapy resulted in a rapid elevation in serum transferrin iron saturation from 11 +/- 1.5% to 80 +/- 7.2% (p < 0.0001), but it decreased to pre-treatment levels within 2 weeks after discontinuation of iron therapy. Serum ferritin concentration increased from 157 +/- 73 mg/l to 434 +/- 105 mg/l during iron therapy (p < 0.0001). In spite of this only 4 patients (2 rHuEPO treated) responded and had a hemoglobin increment > 10 g/l. In the whole group serum transferrin receptor (TfR) levels remained stable, but increased after the cessation of iron dextran only in the rHuEPO treated patients (p < 0.01). In the responders the TfR levels were higher during iron therapy than in the nonresponders (p < 0.02). In an attempt to explain the resistance to iron therapy, serum concentrations of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1b (IL-1b) were also analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iron availability is transiently improved by intravenous iron medication in patients on chronic hemodialysis. 861 62

Ferritin is a ubiquitously distributed iron-binding protein that plays a key role in cellular iron homeostasis. It is composed of two subunits, termed H (heavy or heart) and L (light or liver). In fibroblasts and other cells, the cytokine tumor necrosis factor-alpha (TNF) specifically induces synthesis of the ferritin H subunit. Using nuclear run-off assays, we demonstrate that this TNF-dependent increase in ferritin H is mediated by a selective increase in ferritin H transcription. Transfection of murine fibroblasts with chimeric genes containing the 5'-flanking region of murine ferritin H fused to the human growth hormone reporter gene reveals that the cis-acting element that mediates this response is located approximately 4.8 kilobases distal to the start site of transcription. Deletion analyses delimit the TNF-responsive region to a 40-nucleotide sequence located between nucleotides -4776 and -4736, which we term FER-2. Electrophoretic mobility shift assays and site-specific mutations indicate that this region contains two independent elements: one contains a sequence that binds a member of the NF-kappa B family of transcription factors, and a second contains a novel sequence that partially conforms to the NF-kappa B consensus sequence and may bind a different member of the NF-kappa B/Rel transcription factor family. Thus, effects of an inflammatory cytokine on ferritin are mediated by a family of transcription factors responsive to oxidative stress.
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PMID:Role for NF-kappa B in the regulation of ferritin H by tumor necrosis factor-alpha. 779 15

To examine RNA/protein synthesis of neutrophils and related dynamic changes during the inflammatory process, we investigated mRNA expressions in neutrophils, by RNA blot hybridization analyses using 12 different rabbit gene probes. We first selected five candidate genes encoding inflammation-related proteins, i.e. tumor necrosis factor (TNF-alpha) IL-1 alpha, IL-1 beta, neutrophil activating peptide-1/IL-8 (NAP-1/IL-8) and monocyte chemoattractant protein (MCP)-1. We further selected several genes on basis of the results from gene subtraction between cDNA libraries from neutrophils at an early (5 h) and at a late (24 h) stage of casein-induced acute peritonitis in rabbits, i.e. immune activation gene-2 (Act-2), migration inhibitory factor-related protein-8 (MRP-8), MRP-14, gamma-actin, and formyl-methionyl-leucyl-phenylalanine receptor (fMLP-R), and ferritin light (L) chain. In addition to these genes we used ferritin heavy (H) chain gene, another component of the ferritin molecule. We examined mRNA expressions by cytoplasmic slot blot analysis of the above 12 genes in neutrophils obtained from blood and from various stages of casein-induced inflammation in rabbits. The observed patterns of mRNA expression kinetics were classified into three. Pattern 1: mRNAs of MRP-8, MRP-14, and gamma-actin were constitutively expressed in blood neutrophils, and increased rapidly after emigration into inflammatory sites. Pattern 2: mRNAs of IL-1 beta, NAP-1/IL-8, Act-2, and fMLP-R were undetectable in blood neutrophils, and were induced rapidly after the onset of inflammation. Pattern 3 mRNAs of ferritin L and H chain were induced slowly, and increased with progression of the inflammatory process.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dynamic changes in mRNA expression of neutrophils during the course of acute inflammation in rabbits. 814 23


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