0000000000471505

AUTHOR

Michael P. Pieper

showing 9 related works from this author

Acetylcholine leads to signal transducer and activator of transcription 1 (STAT-1) mediated oxidative/nitrosative stress in human bronchial epithelia…

2013

AbstractThe induction of nitric oxide synthase (iNOS) expression via the signal transducer and activator of transcription 1 (STAT-1) is involved in the mechanism of oxidative/nitrosative stress. We investigated whether acetylcholine (ACh) generates oxidative/nitrosative stress in bronchial epithelial cells during airway inflammation of COPD and evaluated the effects of Tiotropium, a once-daily antimuscarinic drug, and Olodaterol, a long-acting β2-agonist on these mechanisms. Human bronchial epithelial cells (16-HBE) were stimulated (4h, 37°C) with induced sputum supernatants (ISSs) from healthy controls (HC) (n=10), healthy smokers (HS) (n=10) or COPD patients (n=10), as well as with ACh (f…

Malemedicine.medical_specialtyBlotting WesternNitric Oxide Synthase Type IIBronchiOxidative phosphorylationCholinergic AgonistsFlow cytometrychemistry.chemical_compoundPulmonary Disease Chronic ObstructiveWestern blotInternal medicinemedicineHumansRNA Small InterferingMolecular BiologyCells Culturedchemistry.chemical_classificationReactive oxygen speciesbiologymedicine.diagnostic_testNitrotyrosineEpithelial CellsMiddle AgedAcetylcholinerespiratory tract diseasesEpithelial cellNitric oxide synthaseOxidative StressEndocrinologySTAT1 Transcription FactorchemistrySTAT proteinbiology.proteinOxidative/nitrosative stressTyrosineMolecular MedicineSTAT-1FemaleReactive Oxygen SpeciesAcetylcholinemedicine.drugBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
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The pharmacological rationale for combining muscarinic receptor antagonists and beta-adrenoceptor agonists in the treatment of airway and bladder dis…

2014

Highlights • Muscarinic receptors increase smooth muscle tone in airways and urinary bladder. • β-Adrenoceptors relax smooth muscle tone and oppose muscarinic contraction. • Opposition involves transmitter release, signal transduction and receptor expression. • This supports the combined use of muscarinic antagonists and β-adrenoceptor agonists.

medicine.medical_specialtyUrologyDiseaseMuscarinic AntagonistsPharmacologyArticleβ adrenoceptorchemistry.chemical_compoundInternal medicineReceptors Adrenergic betaMuscarinic acetylcholine receptorDrug DiscoveryMuscarinic acetylcholine receptor M4RAT URINARY-BLADDERMedicineAnimalsHumansCyclic adenosine monophosphateADRENERGIC RELAXATIONLung Diseases ObstructivePROTEIN-KINASE-CReceptorTRACHEAL SMOOTH-MUSCLEPharmacologybusiness.industryUrinary Bladder DiseasesMuscarinic acetylcholine receptor M3Muscarinic acetylcholine receptor M2ACETYLCHOLINE-RELEASEAdrenergic beta-Agonistsmedicine.diseaseReceptors MuscarinicEndocrinologyNONNEURONAL CHOLINERGIC SYSTEMchemistryGUINEA-PIG TRACHEADrug Therapy CombinationCYCLIC ADENOSINE-MONOPHOSPHATECA2+-ACTIVATED K+ CHANNELAirwaybusinessUrinary bladder diseaseAUTORADIOGRAPHIC VISUALIZATIONAcetylcholinemedicine.drug
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β2 long-acting and anticholinergic drugs control TGF-β1-mediated neutrophilic inflammation in COPD

2012

AbstractWe quantified TGF-β1 and acetylcholine (ACh) concentrations in induced sputum supernatants (ISSs) from 18 healthy controls (HC), 22 healthy smokers (HS) and 21 COPDs. ISSs from HC, HS and COPD as well as rhTGF-β1 were also tested in neutrophil adhesion and in mAChR2, mAChR3 and ChAT expression experiments in human bronchial epithelial cells (16-HBE). Finally, we evaluated the effects of Olodaterol (a novel inhaled β2-adrenoceptor agonist) and Tiotropium Spiriva®, alone or in combination, on neutrophil adhesion and mAChRs and ChAT expression in stimulated 16-HBE. The results showed that 1) TGF-β1 and ACh concentrations are increased in ISSs from COPD in comparison to HC and HS, and T…

Agonistmedicine.medical_specialtymedicine.drug_classchemistry.chemical_compoundInternal medicineTGF-β1Anticholinergic drugMuscarinic acetylcholine receptormedicineCOPDReceptorMolecular BiologyBeta2 long actingCOPDChemistryOlodaterolTiotropium bromidemedicine.diseaserespiratory tract diseasesEndocrinologyMolecular MedicineNeutrophilic inflammationBronchoconstrictionmedicine.symptomAcetylcholinemedicine.drugBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
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Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients.

2014

T-lymphocytes, including Th17-cells and T-cells expressing acetylcholine (ACh), are key components of systemic inflammation in chronic obstructive pulmonary disease (COPD). We investigated whether ACh promotes Th17 cells in COPD. ACh, IL-17A, IL-22, RORγt, FOXP3 expression and AChIL-17A, AChIL-22, AChRORγt coexpression was evaluated in peripheral blood mononuclear cells (PBMC) from COPD patients (n=16), healthy smokers (HS) (n=12) and healthy control subjects (HC) (n=13) (cultured for 48 h with PMA) by flow cytometry. Furthermore, we studied the effect of Tiotropium (Spiriva®) (100 nM) and Olodaterol (1nM) alone or in combination, and of hemicholinium-3 (50 μM) on AChIL-17A, AChIL-22, AChRO…

MaleImmunologyIntracellular SpaceScopolamine DerivativesPharmacologySystemic inflammationPeripheral blood mononuclear cellCholinergic AntagonistsFlow cytometrychemistry.chemical_compoundPulmonary Disease Chronic ObstructiveRAR-related orphan receptor gammaRisk FactorsmedicineImmunology and AllergyHumansTiotropium BromideAgedAged 80 and overCOPDmedicine.diagnostic_testbusiness.industryInterleukinsOlodaterolInterleukin-17FOXP3Forkhead Transcription FactorsHematologyMiddle AgedNuclear Receptor Subfamily 1 Group F Member 3medicine.diseaseAcetylcholineBenzoxazineschemistryLeukocytes MononuclearTh17 CellsFemalemedicine.symptombusinessAcetylcholinemedicine.drugImmunobiology
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Acetylcholine mediates the release of IL-8 in human bronchial epithelial cells by a NFkB/ERK-dependent mechanism

2007

Acetylcholine may play a role in cell activation and airway inflammation. We evaluated the levels of both mRNA and protein of muscarinic M(1), M(2), M(3) receptors in human bronchial epithelial cell line (16HBE). 16HBE cells were also stimulated with acetylcholine and extracellular signal-regulated kinase1/2 (ERK1/2) and NFkB pathway activation as well as the IL-8 release was assessed in the presence or absence of the inhibitor of Protein-kinase (PKC) (GF109203X), of the inhibitor of mitogenic activated protein-kinase kinase (MAPKK) (PDO9805), of the inhibitor of kinaseB-alpha phosphorilation (pIkBalpha) (BAY11-7082), and of muscarinic receptor antagonists tiotropium bromide, 4-Diphenylacet…

medicine.medical_specialtyIndolesNeutrophilsScopolamine DerivativesBronchiMuscarinic AntagonistsBiologyPharmacologyMaleimideschemistry.chemical_compoundPiperidinesInternal medicineNitrilesMuscarinic acetylcholine receptor M5Muscarinic acetylcholine receptormedicineHumansRNA MessengerSulfonesTiotropium BromideProtein Kinase CCell Line TransformedAcetylcholine receptorFlavonoidsMitogen-Activated Protein Kinase 1PharmacologyMitogen-Activated Protein Kinase 3Gallamine TriethiodideInterleukin-8NF-kappa BMuscarinic acetylcholine receptor M3Epithelial CellsMuscarinic acetylcholine receptor M2PirenzepineMuscarinic acetylcholine receptor M1Receptors MuscarinicAcetylcholineChemotaxis LeukocyteEndocrinologychemistryTelenzepineAcetylcholinemedicine.drugEuropean Journal of Pharmacology
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IL-17A induces chromatin remodeling promoting IL-8 release in bronchial epithelial cells: Effect of Tiotropium

2016

Abstract Aims IL-17A plays a key role in the persistence of airway inflammation, oxidative stress, and reduction of steroid-sensitivity in COPD. We studied the effect of IL-17A on chromatin remodeling and IL-8 production. Main methods We measured the levels of IL-8 and IL-17A in induced sputum supernatants (ISS) from healthy controls (HCs), healthy smokers (HSs), and COPD patients by enzyme-linked immunosorbent assay (ELISA). A human bronchial epithelial cell line (16HBE) was stimulated with ISS from HCs, HSs, or COPD subjects. IL-8 was evaluated in 16HBE by Western blot and real-time polymerase chain reaction (PCR). Histone deacetylase 2 (HDAC2), acetyl histone H3 (Ac-His H3) (k9) and inhi…

Bronchial epithelial cell0301 basic medicineHistone Deacetylase 2BronchiBiologyGeneral Biochemistry Genetics and Molecular BiologyChromatin remodelingProinflammatory cytokineHistonesChromatin remodelingAndrologyPulmonary Disease Chronic Obstructive03 medical and health sciencesHistone H3Western blotIL-17AmedicineHumansInterleukin 8Tiotropium BromideGeneral Pharmacology Toxicology and PharmaceuticsCells CulturedCOPDBiochemistry Genetics and Molecular Biology (all)IL-8medicine.diagnostic_testHistone deacetylase 2Chronic obstructive pulmonary diseaseAnti-Inflammatory Agents Non-SteroidalInterleukin-17Interleukin-8SmokingSputumEpithelial CellsGeneral MedicineChromatin Assembly and Disassemblymedicine.diseaserespiratory tract diseases030104 developmental biologyPharmacology Toxicology and Pharmaceutics (all)ImmunologyInterleukin 17human activitiesLife Sciences
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In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD

2011

Novel pharmacological strategies are aimed at the resolution of systemic inflammation in COPD potentiating peripheral blood T-cell (PBT-cell) apoptosis. Although muscarinic acetylcholine receptors (mAChRs) M(3) and choline-acetyltransferase (ChAT) participate in the airway inflammation of COPD, their role in PBT-cell apoptosis remains unexplained. We evaluated in PBT-cells from COPD patients, smoker (S) and control (C) subjects: (1) apoptosis (by annexin V binding), (2) mAChR M(3) and ChAT expression, acetylcholine (ACh)-binding; (3) choline levels in serum and PBT-cells extracts. We tested the effects of Tiotropium (Spiriva(®)) and hemicholinium-3 (HCh-3) on apoptosis, NFκB pathway, caspas…

MaleImmunologyScopolamine DerivativesApoptosisCD8-Positive T-LymphocytesPharmacologySystemic inflammationCholinergic AntagonistsCholineCholine O-AcetyltransferasePulmonary Disease Chronic ObstructiveAnnexinMuscarinic acetylcholine receptormedicineHumansImmunology and AllergyLymphocyte CountTiotropium BromideCaspaseAgedReceptor Muscarinic M3Caspase 8COPDbiologyCaspase 3Systemic inflammation Non-neuronal components of cholinergic system Caspases NF B pathwaybusiness.industryNF-kappa BHematologyTiotropium bromideMiddle Agedmedicine.diseaserespiratory tract diseasesEnzyme ActivationApoptosisbiology.proteinFemalemedicine.symptombusinessAcetylcholineProtein BindingSignal Transductionmedicine.drugImmunobiology
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Cigarette smoke extract activates human bronchial epithelial cells affecting non-neuronal cholinergic system signalling in vitro.

2010

Abstract Aims Acetylcholine (ACh) is synthesized by Choline Acetyl-Transferase (ChAT) that exerts its physiological effects in airway epithelial cells via muscarinic receptor (MR) activation. We evaluate the effect of ACh stimulation on human bronchial epithelial cells (16-HBE) and test whether cigarette smoke extract (CSE) can modify the basal cellular response to ACh affecting the non-neuronal cholinergic system signalling. Main methods ACh stimulated 16-HBE were tested for ACh-binding, Leukotriene B 4 (LTB 4 ) release and ERK1/2 and NFkB pathway activation. Additionally, we investigated all the aforementioned parameters as well as ChAT and MR proteins and mRNA expression and endogenous A…

medicine.medical_specialtyLeukotriene B4Blotting WesternEndogenyStimulationBronchiPharmacologyBiologyComplex MixturesIn Vitro TechniquesLeukotriene B4General Biochemistry Genetics and Molecular BiologyCell LineCholine O-Acetyltransferasechemistry.chemical_compoundInternal medicineSmokeparasitic diseasesMuscarinic acetylcholine receptorTobaccomedicineHumansGeneral Pharmacology Toxicology and PharmaceuticsReceptorExtracellular Signal-Regulated MAP KinasesAnalysis of VarianceReverse Transcriptase Polymerase Chain ReactionNF-kappa BCholine Acetyl-TransferaseAcetylcholine muscarinic receptorhuman bronchial epithelial cellsGeneral MedicineFlow CytometryCholine acetyltransferaseReceptors MuscarinicAcetylcholineEndocrinologychemistryGene Expression RegulationTelenzepineAcetylcholinemedicine.drugSignal Transduction
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Cigarette smoke alters non-neuronal cholinergic system components inducing MUC5AC production in the H292 cell line.

2013

Abstract Cigarette smoke extract (CSE) affects the expression of Choline Acetyl-Transferase (ChAT), muscarinic acetylcholine receptors, and mucin production in bronchial epithelial cells. Mucin 5AC (MUC5AC), muscarinic acetylcholine receptor M3, ChAT expression, acetylcholine levels and acetylcholine binding were measured in a human pulmonary mucoepidermoid carcinoma cell line (H292) stimulated with CSE. We performed ChAT/RNA interference experiments in H292 cells stimulated with CSE to study the role of ChAT/acetylcholine in MUC5AC production. The effects of Hemicholinium-3 (HCh-3) (50 μM) (a potent and selective choline uptake blocker) and Tiotropium bromide (Spiriva ® ) (100 nM), alone o…

medicine.medical_specialtyScopolamine DerivativesBronchiComplex MixturesMucin 5ACCholinergic AntagonistsCholine O-Acetyltransferasechemistry.chemical_compoundAcetylcholine bindingInternal medicineCell Line TumorSmokeparasitic diseasesMuscarinic acetylcholine receptorTobaccomedicineCholineHumansSecretionAlbuterolNeurotransmitter Uptake InhibitorsTiotropium BromideAutocrine signallingSalmeterol XinafoatePharmacologyReceptor Muscarinic M3Epithelial CellsHemicholinium 3respiratory systemCholine acetyltransferaseAcetylcholineBronchodilator AgentsAndrostadienesEndocrinologychemistryCell cultureFluticasoneRNA InterferenceAcetylcholinemedicine.drugEuropean journal of pharmacology
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