Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11684 (Uteroglobin)
 114 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uteroglobin (UG) gene encodes a cytokine-like, multifunctional, antiinflammatory protein, with potent phospholipase A2-inhibitory activity. It has been suggested that during implantation this protein protects the embryos from maternal immunological assault, facilitates the maintenance of quiescence in the uterus throughout pregnancy, prevents the onset of premature labor, and helps maintain an inflammation-free respiratory organ. This latter function of UG is suggested to be accomplished by preventing hydrolysis of surfactant phospholipids by a lung-specific phospholipase A2. Using reverse transcription polymerase chain reaction, in situ hybridization, immunofluorescence, and radioimmunoassay, we studied UG gene expression in the rabbit uterus throughout gestation and in the fetal lung. Here, we report that: (a) contrary to previous reports, UG gene expression in the rabbit uterus occurs throughout gestation with a precipitous decline just before parturition; (b) this gene expression is dramatically increased in the fetal lung with increasing gestational age; and (c) while there is an inverse relationship between the levels of UG, PGE2, and PGF2 alpha, a positive correlation was found in that of UG and leukotriene C4 in the fetal lung. Our results raise the possibility that dysregulation of UG gene expression, at least in part, may contribute to the onset of premature labor and the development of inflammatory lung disease in premature neonates.
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PMID:Uteroglobin gene expression in the rabbit uterus throughout gestation and in the fetal lung. Relationship between uteroglobin and eicosanoid levels in the developing fetal lung. 761 4

Uteroglobin is a progesterone binding protein, a member of the antiflammin gene family and possibly a novel cytokine. Initially, uteroglobin was identified as the major protein of rabbit uterine secretion during the phase of preimplantation. Counterparts of the rabbit uteroglobin or its gene are described in rat, mouse, hamster, hare, pig, horse and human. While uteroglobin appears as one of the most extensively studied proteins, particularly its physico-chemical properties, including its crystal structure and its gene, the true physiological role of this protein still remains to be unravelled. Essential to understanding the significance of human uteroglobin in reproductive organs, particularly in the endometrium, is a knowledge of the spatial and chronological expression of this secretory protein. Our studies on 115 volunteers combined reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and quantitative assessment by an enzyme-linked immunosorbent assay for uteroglobin. The expression, localization and release of uteroglobulin in the human endometrium are presented. Secretory uteroglobin is found in endometrial tissue homogenates in highest levels of expression during the early luteal phase (days 15-19, 340 pg/mg total protein). In turn, uteroglobin is released into the uterine lumen in peak amounts during the receptive phase of the menstrual cycle (mid-luteal phase, days 20-23, secretion level 833.4 pg/mg total protein). Our immunohistochemical studies match with these results, as uteroglobin is located during the early and mid-luteal phase in the apical compartments of endometrial gland cells. These observations strongly suggest an involvement of uteroglobin in endometrial preparations for implantation.
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PMID:Expression of uteroglobin in the human endometrium. 1058 71

Uteroglobin, a steroid-inducible, cytokine-like, secreted protein with immunomodulatory properties, has been reported to bind progesterone, polychlorinated biphenyls (PCB), and retinol. Structural studies may delineate whether binding of ligands is a likely physiological function of human uteroglobin (hUG). We report a refined crystal structure of uncomplexed recombinant hUG (rhUG) at 2.5-A resolution and the results of our molecular modeling studies of ligand binding to the central hydrophobic cavity of rhUG. The crystal structure of rhUG is very similar to that of reported crystal structures of uteroglobins. Using molecular modeling techniques, the three ligands--PCB, progesterone, and retinol--were docked into the hydrophobic cavity of the dimer structure of rhUG. We undocked the progesterone ligand by pulling the ligand from the cavity into the solvent. From our modeling and undocking studies of progesterone, it is clear that these types of hydrophobic ligands could slip into the cavity between helix-3 and helix-3' of the dimer instead of between helix-1 and helix-4 of the monomer, as proposed earlier. Our results suggest that at least one of the physiological functions of UG is to bind to hydrophobic ligands, such as progesterone and retinol.
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PMID:Crystal structure analysis of recombinant human uteroglobin and molecular modeling of ligand binding. 1119 50

Immunoglobulin A (IgA) nephropathy results from the abnormal deposition of IgA in the renal mesangium. Genetic factors may be involved in the development and progression of IgA nephropathy. Uteroglobin (UG) is a steroid-inducible, cytokine-like, multifunctional protein with anti-inflammatory and immunomodulatory properties. The knockout or antisense mouse of the UG gene develops renal disease similar to IgA nephropathy. We analyzed the UG gene as a candidate for a predisposing factor in 61 Japanese patients with IgA nephropathy (23 children, 38 adults) and detected only the G38A mutation. The gene frequency of the G38A mutation in patients was 0.43, not significantly different from the frequency of 0.36 in healthy controls. However, the frequency of patients homozygous for G38A was twice that of controls, and a significant increase was seen in child patients. We measured serum UG levels in patients and healthy adults. A significant decrease in serum UG levels in homozygotes of G38A compared with homozygotes of G38 was detected only in adult women patients and controls. There is no information on where serum UG is produced or how UG may work in association with IgA nephropathy. However, it is possible that the effect of G38A may be apparent under such stimulation as sex steroids or infections, and homozygotes of the G38A mutation cannot produce sufficient UG in response to stimulation and may be predisposed to IgA nephropathy, especially in childhood.
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PMID:Association of the uteroglobin gene polymorphism with IgA nephropathy. 1177 99

Uteroglobin (UG) or Clara cell protein (CC16), the main secretory product of bronchiolar Clara cells, plays an important protective role in the respiratory tract against inflammatory processes. In the lung, protein secretion is regulated by glucocorticoids, but also proinflammatory cytokines, such as interferon-gamma (IFN-gamma) and TNF-alpha, have been found to modulate the expression of this peptide. We have previously demonstrated that the acute exposure to an organophosphoreted insecticide induces an enhanced production of UG/CC16 by Clara cells. In the present report, we worked with intact and adrenalectomised (ADX) animals to study the mechanism involved in the UG/CC16 increase caused by the insecticide and the role played by a glucocorticoid (dexamethasone; DEX). In intact rats we found that DEX treatment could not reproduce such an increase of UG/CC16 synthesis with pharmacological doses. In ADX rats, even though glucocorticoid deprivation provoked a strong inhibition of UG/CC16 synthesis, the exposure to the organophosphoreted insecticide stimulated the synthesis of the protein, shown by the great accumulation of secretory granules in the cytoplasm of Clara cells and the increase of UG/CC16 detected by immunocytochemistry and western blot. These results imply that glucocorticoids are not essential to trigger the increase of UG/CC16 in response to an injury, and they also suggest an involvement of other molecules associated with inflammation. In coincidence with these observations, we have found that IFN-gamma, a proinflammatory cytokine, increased after insecticide exposition in both groups, intact and ADX, mainly in ADX rats. The stimulation of UG/CC16 synthesis occurring during inflammatory processes of the respiratory tract caused by acute inhalation of a toxicant appears to be functional without the intervention of glucocorticoids and mediated by IFN-gamma as a mechanism for local control of the inflammatory response.
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PMID:Regulation of uteroglobin/Clara cell protein expression after acute lung exposure to an organophosphoreted insecticide. 1283 27

Uteroglobin (UG) is an antiinflammatory protein secreted by the epithelial lining of all organs communicating with the external environment. We reported previously that UG-knockout mice manifest exaggerated inflammatory response to allergen, characterized by increased eotaxin and Th2 cytokine gene expression, and eosinophil infiltration in the lungs. In this study, we uncovered that the airway epithelia of these mice also express high levels of cyclooxygenase (COX)-2, a key enzyme for the production of proinflammatory lipid mediators, and the bronchoalveolar lavage fluid (BALF) contain elevated levels of prostaglandin D2. These effects are abrogated by recombinant UG treatment. Although it has been reported that prostaglandin D2 mediates allergic inflammation via its receptor, DP, neither the molecular mechanism(s) of DP signaling nor the mechanism by which UG suppresses DP-mediated inflammatory response are clearly understood. Here we report that DP signaling is mediated via p38 mitogen-activated protein kinase, p44/42 mitogen-activated protein kinase, and protein kinase C pathways in a cell type-specific manner leading to nuclear factor-kappaB activation stimulating COX-2 gene expression. Further, we found that recombinant UG blocks DP-mediated nuclear factor-kappaB activation and suppresses COX-2 gene expression. We propose that UG is an essential component of a novel innate homeostatic mechanism in the mammalian airways to repress allergen-induced inflammatory responses.
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PMID:Uteroglobin represses allergen-induced inflammatory response by blocking PGD2 receptor-mediated functions. 1514 33

Serum amyloid A (SAA) production is increased by inflamed arthritic synovial tissue, where it acts as a cytokine/chemoattractant for inflammatory and immune cells and as an inducer of matrix degrading enzymes. SAA has been shown to bind lipoxin A4 receptor, a member of the formyl-peptide related 2 G-protein coupled receptor family (ALX) and elicit proinflammatory activities in human primary fibroblast-like synoviocytes (FLS). We report on the identification of uteroglobin, a small globular protein with potent anti-inflammatory activities, as a possible ligand of ALX. Uteroglobin-specific association with ALX was demonstrated by an enzyme immunoassay experiment employing a cell line engineered to express the human ALX receptor. Uteroglobin's interaction with ALX resulted in the inhibition of SAA responses, such as attenuation of phospholipase A2 activation and cellular chemotaxis. In FLS, uteroglobin showed an antagonism against SAA-induced interleukin-8 release and decreased cell migration. These novel roles described for uteroglobin via ALX may help elucidate genetic and clinical observations indicating that a polymorphism in the uteroglobin promoter is linked to disease outcome, specifically prediction of bone erosion in patients with rheumatoid arthritis or severity of IgA glomerulonephritis and sarcoidosis.
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PMID:Uteroglobin, a possible ligand of the lipoxin receptor inhibits serum amyloid A-driven inflammation. 2478 97