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

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

Uteroglobin (UG, Clara cell secretory protein) is a steroid inducible, multifunctional protein that is secreted by the mucosal epithelia. UG has anti-proliferative and anti-metastatic effects in cancer cells. COX-2, which catalyzes the first step in the synthesis of prostanoids, has been shown to be overexpressed in tumors. This study investigated the effect of UG on the inhibition of COX-2 expression in lung cancer cells. The level of the COX-2 protein and its mRNA were decreased by UG, as demonstrated by Western blot and the RT-PCR, respectively. The EIA shows that UG suppressed PGE2 synthesis. Western blot showed that the NF-kappaB nuclear translocation was inhibited by the transduction of UG. In addition, an EMSA demonstrated the inhibition of the NF-kappaB-DNA binding by UG. The luciferase assay showed that UG also inhibited the NF-kappaB-mediated transcription activity. Furthermore, transfection of the lung cancer cell lines with the COX-2 reporter gene constructs demonstrated that the transcription of COX-2 gene was suppressed by UG. These results show that the inhibition of COX-2 expression by UG transduction correlated with the suppression of NF-kappaB activity in the lung cancer cells. This suggests that UG have the possibility for the treatment of lung cancer.
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PMID:Adenovirus-uteroglobin suppresses COX-2 expression via inhibition of NF-kappaB activity in lung cancer cells. 1582 19

An efficient molecular simulation methodology has been developed to determine the positioning of water molecules in the binding site of a protein or protein-ligand complex. Occupancies and absolute binding free energies of water molecules are computed using a statistical thermodynamics approach. The methodology, referred to as Just Add Water Molecules (JAWS), features "theta-water" molecules that can appear and disappear on a binding-site grid. Key approximations render the technique far more efficient than conventional free energy simulations. Testing of JAWS on five diverse examples (neuraminidase, scytalone dehydratase, major urinary protein 1, beta-lactoglobulin, and COX-2) demonstrates its accuracy in locating hydration sites in comparison to results from high-resolution crystal structures. Possible applications include aid in refinement of protein crystal structures, drug lead optimization, setup of docking calculations, and simulations of protein-ligand complexes.
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PMID:Prediction of the water content in protein binding sites. 1975 86