0000000000292905

AUTHOR

Gerd A. Kullak-ublick

showing 4 related works from this author

Hypoxia Positively Regulates the Expression of pH-Sensing G-Protein–Coupled Receptor OGR1 (GPR68)

2016

Background & Aims: A novel family of proton-sensing G-proteinâcoupled receptors, including ovarian cancer G-proteinâcoupled receptor 1 (OGR1) (GPR68) has been identified to play a role in pH homeostasis. Hypoxia is known to change tissue pH as a result of anaerobic glucose metabolism through the stabilization of hypoxia-inducible factor-1α. We investigated how hypoxia regulates the expression of OGR1 in the intestinal mucosa and associated cells. Methods: OGR1 expression in murine tumors, human colonic tissue, and myeloid cells was determined by quantitative reverse-transcription polymerase chain reaction. The influence of hypoxia on OGR1 expression was studied in monocytes/macrophages and…

WT wild type0301 basic medicineMM6 MonoMac 6HV healthy volunteerSPARC secreted protein acidic and rich in cysteineNF-κB nuclear factor-κBInflammationBiologyIEC intestinal epithelial cell03 medical and health sciencesIntestinal mucosaTDAG8Ovarian Cancer G-Protein–Coupled ReceptormedicineOGR1 ovarian cancer G-protein–coupled receptor 1 (GPR68)IFN interferonlcsh:RC799-869ReceptorOriginal ResearchTh T-helperInflammationTNF tumor necrosis factorIBD inflammatory bowel diseaseHepatologyRT-qPCR quantitative reverse-transcription polymerase chain reactionAICAR 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranosideTDAG8 T-cell death-associated gene 8 (GPR65)Inflammatory Bowel DiseaseGRP65GastroenterologyHypoxia (medical)Molecular biologyGPR G-protein–coupled receptormRNA messenger RNAIL interleukinChIP chromatin immunoprecipitationHIF hypoxia-inducible factorUC ulcerative colitis030104 developmental biologyHypoxia-inducible factorsCancer researchCD Crohn's diseaselcsh:Diseases of the digestive system. GastroenterologyTumor necrosis factor alphaFCS fetal calf serummedicine.symptomChromatin immunoprecipitationHomeostasisCellular and Molecular Gastroenterology and Hepatology
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Anti-inflammatory Function of High-Density Lipoproteins via Autophagy of IκB Kinase

2015

Background & Aims: Plasma levels of high-density lipoprotein (HDL) cholesterol are frequently found decreased in patients with inflammatory bowel disease (IBD). Therefore, and because HDL exerts anti-inflammatory activities, we investigated whether HDL and its major protein component apolipoprotein A-I (apoA-I) modulate mucosal inflammatory responses in vitro and in vivo. Methods: The human intestinal epithelial cell line T84 was used as the in vitro model for measuring the effects of HDL on the expression and secretion of tumor necrosis factor (TNF), interleukin-8 (IL-8), and intracellular adhesion molecule (ICAM). Nuclear factor-κB (NF-κB)-responsive promoter activity was studied by …

WT wild typeApolipoprotein BEMSA electrophoretic mobility shift assayMPO myeloperoxidaseIκB kinaseDSS dextran sodium sulphatemTOR the mammalian target of rapamycinRT-PCR real-time polymerase chain reactionNF-κBchemistry.chemical_compound540 ChemistryApoA-I apolipoprotein A-I10038 Institute of Clinical ChemistryOriginal ResearchTNF tumor necrosis factorbiologyIBD inflammatory bowel diseaseChemistryGastroenterologyMyeloperoxidase10076 Center for Integrative Human PhysiologyMEICS murine endoscopic index of colitis severityTumor necrosis factor alphalipids (amino acids peptides and proteins)3-MA 3-methyl adenineNF-κB nuclear factor κBHDL high-density lipoproteinLC3II light chain 3 IIPBS phosphate-buffered salinep-IKK phosphorylated IκB kinase610 Medicine & healthICAM intracellular adhesion molecule246-Trinitrobenzenesulfonic acidTg transgenicmedicineAutophagyCD Crohn’s disease2715 GastroenterologyColitislcsh:RC799-869KO knockoutHepatologyApolipoprotein A-IAutophagyInflammatory Bowel DiseaseTNBS 246-trinitrobenzenesulfonic acidmedicine.diseaseMolecular biologyIL interleukinsiRNA small interfering RNAPI-3 phosphatidylinositol-3Immunologybiology.protein2721 Hepatologylcsh:Diseases of the digestive system. GastroenterologyPFA paraformaldehydeLipoproteinDAPI 4′6-diamidino-2-phenylindoleCMGH Cellular and Molecular Gastroenterology and Hepatology
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use…

2013

This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in…

MAPK/ERK pathwayHealth Toxicology and MutagenesisNF-KAPPA-BReceptors Cytoplasmic and NuclearReview ArticlePharmacologyToxicologyToxicogeneticsNon-parenchymal cells0302 clinical medicineInduced pluripotent stem cellANION-TRANSPORTING POLYPEPTIDECONSTITUTIVE ANDROSTANE RECEPTOR0303 health sciencesGeneral Medicine3. Good healthCell biologymedicine.anatomical_structureLiver030220 oncology & carcinogenesisHepatocyte[SDV.TOX]Life Sciences [q-bio]/ToxicologyInactivation MetabolicClearanceDILIStem cellPLURIPOTENT STEM-CELLSFARNESOID-X-RECEPTORSignal TransductionMechanisms of gene regulationARYL-HYDROCARBON RECEPTORCell signalingPharmacology and ToxicologyHEPATIC STELLATE CELLSBiology03 medical and health sciencesOrgan Culture TechniquesIn vivoCulture TechniquesToxicity TestsmedicineMathematical modeling.AnimalsHumansLiver X receptorDRUG-DRUG INTERACTIONS030304 developmental biologyCryopreservation[INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation3D ModelsCoculture TechniquesHigh-Throughput Screening AssaysSALT EXPORT PUMPGene Expression RegulationHepatic stellate cellHepatocytes[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/PharmacologyPRIMARY RAT HEPATOCYTESMathematical modeling
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

2010

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with gen…

Candidate geneGenetic LinkagePROTEINGenome-wide association studyInflammatory bowel diseaseGenomeACTIVATION0302 clinical medicineCrohn DiseaseSEQUENCE VARIANTSGenetics0303 health sciencesGenomeNEDD4 FAMILYCOMMON VARIANTSASSOCIATION3. Good health030220 oncology & carcinogenesis10076 Center for Integrative Human PhysiologyComputational Biology; Crohn Disease; Genetic Linkage; Genetic Loci; Genetic Variation; Genome Human; Humans; Reproducibility of Results; Genetic Predisposition to Disease; Genome-Wide Association Study; Geneticsinflammatory-bowel-disease sequence variants common variants nedd4 family association gene identification receptor protein activationHuman/dk/atira/pure/subjectarea/asjc/1300/1311Locus (genetics)610 Medicine & healthBiology03 medical and health sciences1311 GeneticsGenetic linkagemedicineGeneticsHumansGenetic Predisposition to Disease030304 developmental biologyGenetic associationIDENTIFICATIONRECEPTORComputational BiologyGenetic VariationReproducibility of Resultsmedicine.diseaseGENESettore MED/03 - Genetica Medica10199 Clinic for Clinical Pharmacology and ToxicologyGenetic Loci570 Life sciences; biologyHuman genomegenome-wide scan.meta-analysis.crohn's diseaseGenome-Wide Association StudyINFLAMMATORY-BOWEL-DISEASE
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