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)

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

Interleukin 1 alpha (IL-1) and tumor necrosis factor alpha (TNF) are two monokines which play a prominent role in the response to inflammation and injury. We recently observed that TNF leads to an increase in the synthesis of the heavy chain of ferritin, suggesting that TNF may be involved in iron homeostasis (Torti et al. (1988) J. Biol. Chem. 263, 12638-12644). The experiments reported here demonstrate that in cultured human muscle cells, IL-1 induces ferritin H mRNA and protein as effectively as TNF. TNF and IL-1 were additive in their effects on ferritin H expression, and IL-1 induction of ferritin H was not blocked by anti-TNF antibodies. Ferritin H induction was a specific response not observed with beta or gamma interferon, nor with transforming growth factor beta. Both differentiated myotubes as well as myoblasts responded to IL-1 with the induction of ferritin H. These results suggest that monokine-mediated alterations in the subunit composition of the ferritin molecule may be of biological relevance in the response to inflammation and injury.
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PMID:Interleukin 1 induces ferritin heavy chain in human muscle cells. 235 Mar 50

The anemia of chronic disease (ACD) is defined as a mild anemia associated with a chronic inflammatory, infectious or neoplastic illness and with a characteristic disturbance of iron metabolism. Many of the findings in ACD can be accounted for by release of a monokine called leukocyte endogenous mediator (LEM), endogenous pyrogen, or interleukin-1. This substance is released from "activated" monocytes. Bacterial endotoxins, certain lymphokines and phagocytic challenges are among the factors stimulating its biosynthesis. LEM induces fever, leukocytosis, biosynthesis. LEM induces fever, leukocytosis, and a variety of biochemical changes, including hypoferremia and alterations in plasma protein synthesis, collectively known as the "acute phase response." It is proposed that ACD results from the long-term elaboration of LEM and that release of this material is the common pathogenetic factor found in the illnesses that are associated with ACD. Some suggestions are made for testing the hypothesis. The hypoferremia associated with ACD is probably caused by defective release of iron from cells--particularly from macrophages, but also from hepatocytes and intestinal epithelium. Two possible mechanisms for this abnormality have been proposed: liberation of lactoferrin from neutrophilic leukocytes and induction of apoferritin synthesis. Neither mechanism has been established. Erythrokinetic studies in ACD have detected a modest reduction of erythrocyte survival without an adequate compensatory increase in the rate of red cell production. The reduced erythrocyte survival is probably related to an increase in phagocytic activity by activated macrophages. Impaired bone marrow response is partly related to the restricted iron supply, but there is substantial evidence for an additional defect in erythropoietin secretion. In some malignant diseases, there is evidence of an additional abnormality: impaired marrow response to a normal amount of erythropoietin. The nature of the erythropoietic defects and the relation of LEM to them remain to be established.
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PMID:The anemia of chronic disease. 634 57

Ferritin inhibition of myelopoiesis has been associated with intrinsic ferroxidase activity of heavy-chain ferritin and with production of a monokine inhibitor of lipopolysaccharide (LPS)-augmented monocytopoiesis. We report here that intrinsic ferroxidase activity of heavy-chain ferritin is required for stimulated production of the monokine inhibitor of LPS-augmented monocytopoiesis.
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PMID:Ferritin stimulation of a monokine inhibitor of lipopolysaccharide-augmented myelopoiesis is ferroxidase dependent. 800 86

A variety of cytokines and chemokines exert potent myelosuppressive effects that play a role in the maintenance of hematopoiesis, which, if unchecked, may result in pathological impairment of blood cell production. Processes that modulate these myelosuppressive effects are not well defined. Here we demonstrate that stromal cell-derived factor-1 (SDF-1/CXCL12), known for its ability to attract and to promote survival of hematopoietic progenitor cells (HPCs) and stem cells, blocks the effects of a broad range of myelosuppressive chemokines on proliferation of HPCs in vitro. The regulatory effects of SDF/CXCL12 on colony formation by mouse bone marrow granulocyte-macrophage (CFUGM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells were assessed. These cells were stimulated to proliferate by combinations of growth factors, such that responses of immature HPCs could be assessed. SDF-1/CXCL12 potently blocked myelosuppressive responses induced by CCL2/MCP-1, CCL3/MIP-1alpha, CCL19/CKbeta-11, CCL25/TECK, CXCL4/PF4, CXCL8/IL-8, CXCL10/IP-10, and XCL1/Lymphotactin. However, SDF/CDL12 did not influence myelosuppression induced by tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, transforming growth factor (TGF)-beta or the iron-binding proteins H-ferritin or lactoferrin (LF). LF, previously shown to suppress release of growth factors, is shown here to also suppress proliferation of immature subsets of HPCs. HPCs from marrows of mice expressing an SDF-1/CXCL12 transgene were insensitive to inhibition by SDF/CXCL12-sensitive myelosuppressive chemokines, but not to SDF/CCL12-insensitive cytokines (TNF-alpha, IFN-gamma, TGF-beta, H-Ferritin, or LF). Thus, SDF-1/CXCL12 differentially and selectively regulates suppression of HPC proliferation by chemokines. These effects may counter myelosuppressive effects of certain chemokines in vivo, where proliferation of HPCs must be sustained.
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PMID:Stromal cell-derived factor-1/CXCL12 selectively counteracts inhibitory effects of myelosuppressive chemokines on hematopoietic progenitor cell proliferation in vitro. 1591 Feb 46

We describe for the first time a case of macrophage activation syndrome in a child with hyperimmunoglobulinemia D with periodic fever syndrome who required intensive care support. Up-regulated monokine production, high serum levels of triglycerides and ferritin, clotting abnormalities with hypofibrinogenemia, and rapidly evolving pancytopenia should alert the clinician to the possible diagnosis of macrophage activation syndrome, even in autoinflammatory diseases characterized basically by the periodic recurrence of unprovoked inflammatory attacks. Bone marrow aspiration showing well-differentiated macrophages phagocytosing hematopoietic elements remains the main tool for a final diagnosis, and cyclosporine is the best strategy for treatment.
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PMID:First report of macrophage activation syndrome in hyperimmunoglobulinemia D with periodic fever syndrome. 1726 1