0000000000700862

AUTHOR

Hiroaki Ito

showing 2 related works from this author

TGF-β Suppresses Tumor Progression in Colon Cancer by Inhibition of IL-6 trans-Signaling

2004

Alterations of TGF-beta signaling have been described in colorectal cancer, although the molecular consequences are largely unknown. By using transgenic mice overexpressing TGF-beta or a dominant-negative TGF-betaRII, we demonstrate that TGF-beta signaling in tumor infiltrating T lymphocytes controls the growth of dysplastic epithelial cells in experimental colorectal cancer, as determined by histology and a novel system for high-resolution chromoendoscopy. At the molecular level, TGF-beta signaling in T cells regulated STAT-3 activation in tumor cells via IL-6. IL-6 signaling required tumor cell-derived soluble IL-6R rather than membrane bound IL-6R and suppression of such TGF-beta-depende…

Genetically modified mouseSTAT3 Transcription FactorColorectal cancerRecombinant Fusion ProteinsT-LymphocytesImmunologyBlotting WesternEnzyme-Linked Immunosorbent AssayMice TransgenicProtein Serine-Threonine KinasesMiceIn vivoTransforming Growth Factor betamedicineImmunology and AllergyAnimalsHumansEndoscopy Digestive SystemIntestinal MucosaInterleukin 6Autocrine signallingMice KnockoutbiologyInterleukin-6Reverse Transcriptase Polymerase Chain ReactionReceptor Transforming Growth Factor-beta Type IIHistologymedicine.diseaseImmunohistochemistryReceptors Interleukin-6DNA-Binding ProteinsDisease Models AnimalInfectious DiseasesTumor progressionImmunologyColonic NeoplasmsCancer researchbiology.proteinDisease ProgressionTrans-ActivatorsReceptors Transforming Growth Factor betaTransforming growth factorSignal TransductionImmunity
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Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells.

2007

We previously reported high levels of the soluble form of the IL-6R (sIL-6R) in the airways of asthmatic subjects. Here, we analyzed the IL-6R effects on Th2 cell survival in the lung by locally antagonizing sIL-6R-mediated trans-signaling with a designer fusion protein (gp130-Fc) as well as IL-6R signaling with an antibody against the gp80 unit of the IL-6R (alphaIL-6R) in a murine model of asthma after ovalbumin peptide (OVA) sensitization and challenge. Blockade of the sIL-6R led to a significant decrease in inflammatory cells by an apoptosis-independent mechanism. In contrast, local treatment with alphaIL-6R antibodies that also block signaling via the membrane-bound IL-6R (mIL-6R) led …

CD4-Positive T-LymphocytesSTAT3 Transcription FactorOvalbuminT cellRecombinant Fusion ProteinsImmunologyGene ExpressionApoptosisBiologyT-Lymphocytes RegulatoryAntibodiesInterleukin 21MicemedicineCytokine Receptor gp130Immunology and AllergyCytotoxic T cellAnimalsIL-2 receptorPhosphorylationLungMice Inbred BALB CInterleukin-6FOXP3Forkhead Transcription FactorsGeneral MedicineT lymphocyterespiratory systemReceptors Interleukin-6AsthmaCoculture TechniquesImmunoglobulin Fc FragmentsDisease Models Animalmedicine.anatomical_structureApoptosisImmunologyCancer researchFemaleImmunizationSignal transductionBronchoalveolar Lavage FluidSignal TransductionInternational immunology
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