Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 6 (IL6) is the new definition of a group of cytokines previously named according to their biological activity, e.g. B cell stimulatory factor 2 (BSF-2), hybridoma plasmocytoma-growth factor (HGF), interferon-beta 2 (IFN-beta 2), hepatocyte stimulating factor (HSF). It has recently been suggested that IL6 may represent the major mediator of acute-phase protein response whereas IL1 beta and TNF-alpha could play a minor role. We compared the effect of the three cytokines on hepatic protein synthesis by performing in vitro as well as in vivo experiments. Human hepatoma cells (PLC/PRF5) were exposed to each cytokine separately for 20 h, and the effect was then studied at the protein and RNA level. All three cytokines reduced albumin and increased C3 and ceruloplasmin biosynthesis. The cytokines induced the same effect at the RNA level indicating that the modulation was pretranslational. The effect of the cytokines was specific since actin gene expression was not changed; furthermore the effect was blocked by specific antibodies against the cytokines. The effect of the single cytokines was dose and time dependent, and quantitatively comparable. None of the cytokines was able to alter alpha 1-anti-trypsin synthesis. In vivo experiments with mice showed that IL1 beta and TNF-alpha both induce serum amyloid A (SAA) mRNA in the mouse liver and increase factor B (Bf) gene expression. Human recombinant IL6 induced SAA gene expression and it also had a weak positive effect on Bf gene expression after i.p. injection. These data demonstrate that the three cytokines studied are quantitatively and qualitatively comparable, and that all three are probably involved in acute-phase protein response.
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PMID:Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha. 313 37

Infection of injury results in several systemic and central reactions termed the acute phase response (APR). Substantial evidence suggests that cytokines induced by microbes initiate the APR. We compared the APR induced in rabbits by a model bacterial stimulus, lipopolysaccharide (LPS), to that induced by a model viral stimulus, polyriboinosinic:polyribocytidylic acid (poly I:C). The cytokine mRNA responses in a mouse macrophage cell line (RAW 264.7) to LPS or poly I:C were also determined. Rabbits were injected intravenously or intracerebroventricularly with different doses of LPS or poly I:C. Colonic temperatures (Tco) and blood samples were taken at the time of injection and at 3, 6, and 24 h after injection. Leukocyte numbers, serum antiviral activity, serum ceruloplasmin, and plasma fibrinogen were analyzed. Both intravenously injected LPS and poly I:C increased Tco, decreased leukocytes, and increased ceruloplasmin. Only LPS by the intravenous route increased fibrinogen, whereas only intravenously injected poly I:C induced antiviral activity. Intracerebroventricular injections of LPS and poly I:C also elicited dose-dependent febrile responses but did not change the hematologic APR significantly except for fibrinogen. The primary distinctions between LPS and poly I:C with respect to cytokine induction in the RAW 264.7 macrophage cell line were that LPS failed to induce interferon (IFN)-alpha, poly I:C induced interleukin (IL)-6 mRNA minimally and for a shorter time period than did LPS, and LPS induced IL-1 alpha and IFN-beta more rapidly than did poly I:C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of acute phase responses induced in rabbits by lipopolysaccharide and double-stranded RNA. 781 Jul 70

Ceruloplasmin is a 132-kDa glycoprotein abundant in human plasma. It has multiple in vitro activities, including copper transport, lipid pro- and antioxidant activity, and oxidation of ferrous ion and aromatic amines; however, its physiologic role is uncertain. Although ceruloplasmin is synthesized primarily by the liver in adult humans, production by cells of monocytic origin has been reported. We here show that IFN-gamma is a potent inducer of ceruloplasmin synthesis by monocytic cells. Activation of human monoblastic leukemia U937 cells with IFN-gamma increased the production of ceruloplasmin by at least 20-fold. The identity of the protein was confirmed by plasmin fingerprinting. IFN-gamma also increased ceruloplasmin mRNA. Induction followed a 2- to 4-h lag and was partially blocked by cycloheximide, indicating a requirement for newly synthesized factors. Ceruloplasmin induction in monocytic cells was agonist specific, as IL-1, IL-4, IL-6, IFN-alpha, IFN-beta, TNF-alpha, and LPS were completely ineffective. The induction was also cell type specific, as IFN-gamma did not induce ceruloplasmin synthesis in endothelial or smooth muscle cells. In contrast, IFN-gamma was stimulatory in other monocytic cells, including THP-1 cells and human peripheral blood monocytes, and also in HepG2 cells. Ceruloplasmin secreted by IFN-gamma-stimulated U937 cells had ferroxidase activity and was, in fact, the only secreted protein with this activity. Monocytic cell-derived ceruloplasmin may contribute to defense responses via its ferroxidase activity, which may drive iron homeostasis in a direction unfavorable to invasive organisms.
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PMID:Induction of ceruloplasmin synthesis by IFN-gamma in human monocytic cells. 925 59