0000000000186349

AUTHOR

Gerhard Rogler

showing 5 related works from this author

Succinate receptor mediates intestinal inflammation and fibrosis.

2018

Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in inflamed areas and its signaling through succinate receptor (SUCNR1) regulates immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease patients and its role in murine intestinal inflammation and fibrosis. We show that both serum and intestinal succinate levels and SUCNR1 expression in intestinal surgical resections were higher in CD patients than in controls. SUCNR1 co-localized with CD86, CD206, and alpha-SMA(+) cells in human intestine and we found a positive and significant correlation between SUCNR1 and alpha-SMA expression. In human isolated fibroblasts from CD patients SUCNR1 expres…

0301 basic medicineAdultMaleAdolescentImmunologyMacrophage polarizationSuccinic Acid610 Medicine & healthProinflammatory cytokineReceptors G-Protein-Coupled03 medical and health sciencesMiceYoung Adult0302 clinical medicineImmune systemCrohn DiseaseFibrosismedicineImmunology and AllergyAnimalsHumansIntestinal MucosaFibroblastReceptorCells CulturedCD86InflammationMice Knockout2403 Immunologybusiness.industryMacrophagesmedicine.diseaseColitisFibrosisCitric acid cycleMice Inbred C57BLDisease Models Animal10219 Clinic for Gastroenterology and Hepatology030104 developmental biologymedicine.anatomical_structure2723 Immunology and AllergyCancer researchFemalebusiness030215 immunologyMucosal immunology
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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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Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis

2016

BACKGROUND Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects. We subsequently investigated the impact of pirfenidone treatment on development of fibrosis in a new mouse model of intestinal fibrosis. METHODS Small bowel resections from donor mice were transplanted subcutaneously into the neck of recipients. Animals received either pirfenidone (100 mg/kg, three times daily, orally) or vehicle. RESULTS After administration of pirfenidone, a signif…

0301 basic medicinemedicine.medical_specialtyPyridonesBlotting Western610 Medicine & healthGastroenterologyImmunoenzyme TechniquesMice03 medical and health sciencesIdiopathic pulmonary fibrosis0302 clinical medicineTransforming Growth Factor betaFibrosis10049 Institute of Pathology and Molecular PathologyInternal medicinemedicineAnimalsImmunology and Allergy2715 GastroenterologyCell ProliferationMice Inbred BALB CbiologyCell growthbusiness.industryAnti-Inflammatory Agents Non-SteroidalGastroenterologyPirfenidoneTransforming growth factor betamedicine.diseaseFibrosisMice Inbred C57BLTransplantationBlotDisease Models AnimalIntestinal Diseases10219 Clinic for Gastroenterology and Hepatology030104 developmental biology2723 Immunology and Allergybiology.proteinFemale030211 gastroenterology & hepatologyCollagen10069 Clinic of Cranio-Maxillofacial SurgerybusinessAfter treatmentmedicine.drugInflammatory Bowel Diseases
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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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Mutant HRAS as novel target for MEK and mTOR inhibitors.

2015

HRAS is a frequently mutated oncogene in cancer. However, mutant HRAS as drug target has not been investigated so far. Here, we show that mutant HRAS hyperactivates the RAS and the mTOR pathway in various cancer cell lines including lung, bladder and esophageal cancer. HRAS mutation sensitized toward growth inhibition by the MEK inhibitors AZD6244, MEK162 and PD0325901. Further, we found that MEK inhibitors induce apoptosis in mutant HRAS cell lines but not in cell lines lacking RAS mutations. In addition, knockdown of HRAS by siRNA blocked cell growth in mutant HRAS cell lines. Inhibition of the PI3K pathway alone or in combination with MEK inhibitors did not alter signaling nor had an imp…

mTOR inhibitorMutantBlotting Western610 Medicine & healthApoptosisMice SCIDCell LineProto-Oncogene Proteins p21(ras)chemistry.chemical_compoundCell Line TumorNeoplasmsMedicineAnimalsHumansHRASHRAS mutationsProtein Kinase InhibitorsPI3K/AKT/mTOR pathwayCell ProliferationGeneticsMitogen-Activated Protein Kinase KinasesMEK inhibitorOncogeneCell growthbusiness.industryMEK inhibitorTOR Serine-Threonine KinasesDiphenylamineXenograft Model Antitumor AssaysTumor Burdenlung cancer10219 Clinic for Gastroenterology and HepatologyCell Transformation NeoplasticOncologychemistry10032 Clinic for Oncology and HematologyBenzamidesMutationCancer researchbladder cancer2730 OncologyBenzimidazolesRNA InterferenceSignal transductionGrowth inhibitionbusinessSignal TransductionResearch PaperOncotarget
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