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

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

Tumor necrosis factor-alpha (TNF-alpha) plays a role in the host's defence against infections with African trypanosomes. It helps to control the blood stream form of the parasite and in Trypanosoma congolense infections, it also prolongs survival. The mechanisms by which this cytokine can influence parasitemia and survival are unknown. Therefore, the levels of acute phase proteins and other inflammatory cytokines were monitored in trypano-tolerant wild-type and TNF-alpha-deficient mice during a T. congolense infection. The titres of ceruloplasmin (CP), alpha1-acid glycoprotein (AGP) and serum amyloid P (SAP) increased and reached their peaks at 11 days post-infection, when the first peak of parasitemia was observed. No significant differences were observed in the acute phase protein profiles between the two mouse strains. Also the profiles of serum titres of IFN-gamma, IL-1alpha, IL-6 and IL-10 were not significantly different. Our present results indicate that acute phase protein and cytokine responses can be induced in the absence of TNF-alpha during a T. congolense infection in mice, and that the susceptibility of the TNF-alpha-deficient mice is not due to modulation of expression of these molecules.
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PMID:The secretion of acute phase proteins and inflammatory cytokines during Trypanosoma congolense infection is not affected by the absence of the TNF-alpha gene. 1530 73

Aminoacyl tRNA synthetases (ARS) catalyze the ligation of amino acids to cognate tRNAs. Chordate ARSs have evolved distinctive features absent from ancestral forms, including compartmentalization in a multisynthetase complex (MSC), noncatalytic peptide appendages, and ancillary functions unrelated to aminoacylation. Here, we show that glutamyl-prolyl-tRNA synthetase (GluProRS), a bifunctional ARS of the MSC, has a regulated, noncanonical activity that blocks synthesis of a specific protein. GluProRS was identified as a component of the interferon (IFN)-gamma-activated inhibitor of translation (GAIT) complex by RNA affinity chromatography using the ceruloplasmin (Cp) GAIT element as ligand. In response to IFN-gamma, GluProRS is phosphorylated and released from the MSC, binds the Cp 3'-untranslated region in an mRNP containing three additional proteins, and silences Cp mRNA translation. Thus, GluProRS has divergent functions in protein synthesis: in the MSC, its aminoacylation activity supports global translation, but translocation of GluProRS to an inflammation-responsive mRNP causes gene-specific translational silencing.
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PMID:Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation. 1547 30

Three experiments were conducted to investigate the effect of dietary glycine (Gly) supplementation on inflammatory responses in broiler chicks fed a basal diet using maize and soybean meal as the primary ingredients. Inflammation-related processes following lipopolysaccharide (LPS) injection were examined by analysing plasma concentrations of nitrate plus nitrite (NOx) and ceruloplasmin (Cer) in experiments 1 and 2, or expression of several genes in the spleen and liver including IL-1 beta and -6, TNF-like ligand (TL)1A, inducible NO synthase, interferon (IFN)-gamma and toll-like receptor (TLR) 4 were examined in experiment 3. Growth performance was also determined following immunological stimulation by both LPS and Sephadex injection in experiment 2. In experiment 1, birds fed a diet supplemented with Gly at 10 or 20 g/kg showed lower responses in plasma NOx and Cer than birds fed the diet supplemented with Gly at 0 or 40 g/kg. In experiment 2, a similar effect of Gly supplementation at 10 g/kg on plasma NOx and Cer was observed when chicks were fed either an isonitrogenous diet with Gly or glutamic acid (Glu). Gly-supplemented diet-fed birds showed better growth performance than Glu-supplemented diet-fed birds. The splenic expression of inflammatory response-related genes in birds fed a diet supplemented with Gly at 10 g/kg diet was lower than that of birds fed the basal diet in experiment 3. These results suggest that dietary Gly supplementation modulates the inflammatory response partly through changes in the expression of pro-inflammatory cytokines such as IL-1, IL-6, IFN-gamma and TL1A.
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PMID:Dietary supplementation of glycine modulates inflammatory response indicators in broiler chickens. 1837 92

The role of chicken TNF-like ligand 1A (ChTL1A) on inflammation and its receptor candidates was investigated to further understand its function as a proinflammatory cytokine. ChTL1A decreased the viability of CHO-K1 cells transfected with chicken TNFR2 or decoy receptor 3 and bound to TNFR2 and decoy receptor 3. ChTL1A was detected in chicken blood samples taken 4 h after LPS injection. Increased mRNA for inflammatory response-related factors such as IL-1beta, IL-6, ChTL1A, IFN-gamma, inducible NO synthase, and cyclooxygenase 2 were found in spleen samples following LPS injection. Ceruloplasmin and alpha(1) acid glycoprotein (as positive acute phase proteins) were increased in chicken plasma 12 h after ChTL1A injection. The injection of anti-ChTL1A Ab was able to prevent typical increases in plasma nitrite plus nitrate, ceruloplasmin, and alpha(1) acid glycoprotein concentrations following LPS injection. These results indicate that ChTL1A is a proinflammatory cytokine in chickens, animals that do not have TNF-alpha and lymphotoxin alpha orthologous genes, and that its proinflammatory action is, at least in part, expressed through binding to TNFR2.
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PMID:Role of chicken TL1A on inflammatory responses and partial characterization of its receptor. 1852 99

The aim of this study was to determine the serum cytokine levels in patients with Wilson's disease (WD) and correlate with phenotype, therapeutic status and laboratory data. In this cross-sectional study, the serum levels of cytokines were estimated in 34 patients (M : F, 23 : 11; drug-naive, 11) with WD (mean age: 13.8 +/- 8.6 and 19.6 +/- 9.03 years) and compared with 30 controls. The following serum cytokines were analysed using enzyme-linked immunosorbent assay: (i) tumour necrosis factor (TNF)-alpha, (ii) interferon (IFN)-gamma, (iii) interleukin (IL)-2, (iv) IL-6 and (v) IL-4. Serum TNF-alpha (P < 0.001), IFN-gamma (P = 0.005) and IL-6 (P < 0.001) were detectable in WD compared with controls. However, serum level elevation of IL-4 (P = 0.49) and IL-2 (P = 0.11), although detectable compared with controls, was statistically insignificant. The disease severity and therapeutic status did not affect the cytokines. Presence of anaemia, leucopenia, thrombocytopenia, pancytopenia and hepatic dysfunction did not influence cytokine levels. There was a significant negative correlation between IL-6 and ceruloplasmin (P = 0.04) and anti-inflammatory cytokines (IL-4) and copper level (P = 0.01). Serum cytokines, both proinflammatory and anti-inflammatory subtypes, were elevated significantly in patients with WD. Further studies would establish their role in its pathogenesis.
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PMID:Do cytokines have any role in Wilson's disease? 1882 41

This study was aimed to evaluate the possible changes caused by a single bout of moderate-intensity exercise in a hot environmental temperature on the immune function and on inflammatory markers. A total of 22 young male adults (VO2(max), 55.4 +/- 3.6 ml x kg(-1) x min(-1)) volunteered to participate in an exercise session of 60 minutes on a treadmill ergometer at moderate speed (60% of the maximum aerobic speed) in hot environmental conditions (35 degrees C and humidity 60%). Total leukocyte numbers, lymphocyte subsets (CD8+, CD4+, CD3+, NK and CD19+), cytokine production capacity by peripheral blood mononuclear cells (PBMCs) (IL-2, IL-4, IL-5, IL-10, IFN-gamma and TNF-alpha) as well as the concentration of several inflammation related proteins (ceruloplasmin, C-reactive protein (CRP), complement factors C3 and C4) were evaluated before and after exercise. The results show that leukocyte and neutrophil absolute values increased (P < 0.001) after the exercise period. In contrast, eosinophil values decreased (P < 0.05) after the exercise. In addition, ceruloplasmin, C3 and C4 values (P < 0.05) increased after exercise. No changes in T lymphocyte subsets, cytokine production, or CRP were observed. These data confirm previous studies suggesting that a 60 min exercise in a hot environment is enough to cause a physiologic adaptation to these special conditions leading to an increase of non-specific immune cells and promoting inflammatory processes. On the other hand, PCR values, lymphocyte subsets and the capacity of cytokine production by PBMC were not changed in a relatively short bout of exercise under these conditions in contrast with previous studies.
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PMID:Immunological changes after a single bout of moderate-intensity exercise in a hot environment. 1924 33