Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313356870> ?p ?o ?g. }
Showing items 1 to 98 of
98
with 100 items per page.
- W4313356870 endingPage "53.5" @default.
- W4313356870 startingPage "53.5" @default.
- W4313356870 abstract "Abstract An important portion of asthmatics do not respond to current therapies. Thus, the need for new therapeutic drugs becomes urgent. We have demonstrated a critical role for PARP in experimental asthma. In the current study, we test the efficacy of Olaparib, a PARP inhibitor, recently introduced in clinical trials against cancer in blocking established asthma traits in animal models of the disease and determine the mechanism by which it achieves such protection. We show that administration of olaparib in mice post-challenge conferred a robust reduction in airway eosinophilia, mucus production and hyperresponsiveness even after repeated challenges with ovalbumin. The protective effects of olaparib were linked to a suppression of Th2 cytokines and ova-specific IgE with an increase in the Th1 cytokine IFN-g. These traits were associated with a decrease in splenic CD4+T cells and concomitant increase in T-regulatory cells. Adoptive transfer of Th2-skewed OT-II-WT CD4+T cells reversed both Th2 and Th1 cytokines and ova-specific IgE production in ovalbumin-challenged naïve PARP-1-/- mice suggesting a role for PARP-1 in CD4+T but not B cells. Our ex vivo studies show that olaparib treatment markedly reduced CD3/CD28-stimulated gata-3 and il4 expression in Th2-skewed CD4+T cells while causing an elevation in t-bet and ifn-g expression in Th1-skewed CD4+T cells. Our findings show the potential of PARP inhibition as a viable therapeutic strategy to be tested in human clinical trials" @default.
- W4313356870 created "2023-01-06" @default.
- W4313356870 creator A5004037751 @default.
- W4313356870 creator A5005601094 @default.
- W4313356870 creator A5008991226 @default.
- W4313356870 creator A5013936643 @default.
- W4313356870 creator A5016671074 @default.
- W4313356870 creator A5017922189 @default.
- W4313356870 creator A5032410036 @default.
- W4313356870 creator A5032576507 @default.
- W4313356870 creator A5036846597 @default.
- W4313356870 creator A5056280960 @default.
- W4313356870 creator A5069329847 @default.
- W4313356870 creator A5071917416 @default.
- W4313356870 creator A5080444742 @default.
- W4313356870 creator A5082208073 @default.
- W4313356870 date "2015-05-01" @default.
- W4313356870 modified "2023-09-27" @default.
- W4313356870 title "PARP inhibition by olaparib or gene knockout blocks asthma manifestation in mice by modulating CD4+ T cell function (HYP2P.324)" @default.
- W4313356870 doi "https://doi.org/10.4049/jimmunol.194.supp.53.5" @default.
- W4313356870 hasPublicationYear "2015" @default.
- W4313356870 type Work @default.
- W4313356870 citedByCount "0" @default.
- W4313356870 crossrefType "journal-article" @default.
- W4313356870 hasAuthorship W4313356870A5004037751 @default.
- W4313356870 hasAuthorship W4313356870A5005601094 @default.
- W4313356870 hasAuthorship W4313356870A5008991226 @default.
- W4313356870 hasAuthorship W4313356870A5013936643 @default.
- W4313356870 hasAuthorship W4313356870A5016671074 @default.
- W4313356870 hasAuthorship W4313356870A5017922189 @default.
- W4313356870 hasAuthorship W4313356870A5032410036 @default.
- W4313356870 hasAuthorship W4313356870A5032576507 @default.
- W4313356870 hasAuthorship W4313356870A5036846597 @default.
- W4313356870 hasAuthorship W4313356870A5056280960 @default.
- W4313356870 hasAuthorship W4313356870A5069329847 @default.
- W4313356870 hasAuthorship W4313356870A5071917416 @default.
- W4313356870 hasAuthorship W4313356870A5080444742 @default.
- W4313356870 hasAuthorship W4313356870A5082208073 @default.
- W4313356870 hasConcept C104317684 @default.
- W4313356870 hasConcept C126322002 @default.
- W4313356870 hasConcept C150903083 @default.
- W4313356870 hasConcept C170493617 @default.
- W4313356870 hasConcept C182704531 @default.
- W4313356870 hasConcept C182979987 @default.
- W4313356870 hasConcept C203014093 @default.
- W4313356870 hasConcept C207001950 @default.
- W4313356870 hasConcept C26291073 @default.
- W4313356870 hasConcept C2776090121 @default.
- W4313356870 hasConcept C2777701055 @default.
- W4313356870 hasConcept C2779138821 @default.
- W4313356870 hasConcept C2779962180 @default.
- W4313356870 hasConcept C502942594 @default.
- W4313356870 hasConcept C55493867 @default.
- W4313356870 hasConcept C71924100 @default.
- W4313356870 hasConcept C82381507 @default.
- W4313356870 hasConcept C86803240 @default.
- W4313356870 hasConcept C8891405 @default.
- W4313356870 hasConcept C90375314 @default.
- W4313356870 hasConceptScore W4313356870C104317684 @default.
- W4313356870 hasConceptScore W4313356870C126322002 @default.
- W4313356870 hasConceptScore W4313356870C150903083 @default.
- W4313356870 hasConceptScore W4313356870C170493617 @default.
- W4313356870 hasConceptScore W4313356870C182704531 @default.
- W4313356870 hasConceptScore W4313356870C182979987 @default.
- W4313356870 hasConceptScore W4313356870C203014093 @default.
- W4313356870 hasConceptScore W4313356870C207001950 @default.
- W4313356870 hasConceptScore W4313356870C26291073 @default.
- W4313356870 hasConceptScore W4313356870C2776090121 @default.
- W4313356870 hasConceptScore W4313356870C2777701055 @default.
- W4313356870 hasConceptScore W4313356870C2779138821 @default.
- W4313356870 hasConceptScore W4313356870C2779962180 @default.
- W4313356870 hasConceptScore W4313356870C502942594 @default.
- W4313356870 hasConceptScore W4313356870C55493867 @default.
- W4313356870 hasConceptScore W4313356870C71924100 @default.
- W4313356870 hasConceptScore W4313356870C82381507 @default.
- W4313356870 hasConceptScore W4313356870C86803240 @default.
- W4313356870 hasConceptScore W4313356870C8891405 @default.
- W4313356870 hasConceptScore W4313356870C90375314 @default.
- W4313356870 hasIssue "1_Supplement" @default.
- W4313356870 hasLocation W43133568701 @default.
- W4313356870 hasOpenAccess W4313356870 @default.
- W4313356870 hasPrimaryLocation W43133568701 @default.
- W4313356870 hasRelatedWork W1506161763 @default.
- W4313356870 hasRelatedWork W2489000876 @default.
- W4313356870 hasRelatedWork W2776352834 @default.
- W4313356870 hasRelatedWork W2953447703 @default.
- W4313356870 hasRelatedWork W3023457002 @default.
- W4313356870 hasRelatedWork W3121450744 @default.
- W4313356870 hasRelatedWork W4313356870 @default.
- W4313356870 hasRelatedWork W4320724591 @default.
- W4313356870 hasRelatedWork W4362493060 @default.
- W4313356870 hasRelatedWork W4362495229 @default.
- W4313356870 hasVolume "194" @default.
- W4313356870 isParatext "false" @default.
- W4313356870 isRetracted "false" @default.
- W4313356870 workType "article" @default.