0000000000770078

AUTHOR

Ulrike Billmeier

showing 3 related works from this author

Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis

2016

Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates…

0301 basic medicineExtracellular TrapsHydrolasesNeutrophilsScienceGeneral Physics and AstronomyBiologyExtracellular TrapsArticleGeneral Biochemistry Genetics and Molecular BiologyMice03 medical and health sciencesPancreatic JuiceProtein-Arginine Deiminase Type 4medicineAnimalsHumansPancreasCeruletideMultidisciplinaryReverse Transcriptase Polymerase Chain ReactionQInterleukin-17Pancreatic DuctsGeneral ChemistryNeutrophil extracellular trapsFlow Cytometrymedicine.diseaseImmunohistochemistryChromatinCell biologyChromatinDisease Models AnimalHistone citrullination030104 developmental biologymedicine.anatomical_structurePancreatitisChronic DiseasePancreatic juiceImmunologyProtein-Arginine DeiminasesCytokinesPancreatitisPancreasCeruletideNature Communications
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Designer Thiopurine-analogues for Optimised Immunosuppression in Inflammatory Bowel Diseases.

2015

Background and Aims: The clinical use of azathioprine and 6-mercaptopurine is limited by their delayed onset of action and potential side effects such as myelosuppression and hepatotoxicity. As these drugs specifically target the Vav1/Rac1 signalling pathway in T lamina propria lymphocytes via their metabolite 6-thio-GTP, we studied expression and optimised suppression of this pathway in inflammatory bowel diseases [IBD]. Methods: Rac1 and Vav1 expressions were analysed in mucosal immune cells in IBD patients. Targeted molecular modelling of the 6-thio-GTP molecule was performed to optimise Rac1 blockade; 44 modified designer thiopurine-analogues were tested for apoptosis induction, potenti…

0301 basic medicinerac1 GTP-Binding Proteinmedicine.medical_treatmentT-LymphocytesAzathioprineApoptosisInflammatory bowel diseaseDesigner Drugs03 medical and health sciences0302 clinical medicineImmune systemIntestinal mucosamedicineHumansIntestinal MucosaProto-Oncogene Proteins c-vavLamina propriaThiopurine methyltransferasebiologybusiness.industryMercaptopurineGastroenterologyImmunosuppressionGeneral Medicinemedicine.diseaseInflammatory Bowel Diseases030104 developmental biologymedicine.anatomical_structureApoptosisCase-Control StudiesDrug DesignImmunologybiology.protein030211 gastroenterology & hepatologybusinessBiomarkersImmunosuppressive Agentsmedicine.drugSignal TransductionJournal of Crohn'scolitis
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Activation of Intestinal Epithelial Stat3 Orchestrates Tissue Defense during Gastrointestinal Infection

2015

Gastrointestinal infections with EHEC and EPEC are responsible for outbreaks of diarrheal diseases and represent a global health problem. Innate first-line-defense mechanisms such as production of mucus and antimicrobial peptides by intestinal epithelial cells are of utmost importance for host control of gastrointestinal infections. For the first time, we directly demonstrate a critical role for Stat3 activation in intestinal epithelial cells upon infection of mice with Citrobacter rodentium - a murine pathogen that mimics human infections with attaching and effacing Escherichia coli. C. rodentium induced transcription of IL-6 and IL-22 in gut samples of mice and was associated with activat…

STAT3 Transcription FactorColonAntimicrobial peptideslcsh:MedicineInflammation-digestive systemMicrobiologyMiceMedizinische FakultätmedicineCitrobacter rodentiumAnimalsHumansddc:610Intestinal Mucosalcsh:ScienceSTAT3PathogenMice KnockoutGastrointestinal tractMultidisciplinarybiologylcsh:REnterobacteriaceae InfectionsEpithelial CellsColitisMucusEpitheliumIntestinesMice Inbred C57BLmedicine.anatomical_structureImmunologybiology.proteinCitrobacter rodentiumlcsh:Qmedicine.symptomResearch ArticlePLoS ONE
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