| First Author | Mothes B | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 7 | Pages | e0159310 |
| PubMed ID | 27442134 | Mgi Jnum | J:282980 |
| Mgi Id | MGI:6254909 | Doi | 10.1371/journal.pone.0159310 |
| Citation | Mothes B, et al. (2016) p110gamma/delta Double-Deficiency Induces Eosinophilia and IgE Production but Protects from OVA-Induced Airway Inflammation. PLoS One 11(7):e0159310 |
| abstractText | The catalytical isoforms p110gamma and p110delta of phosphatidylinositide 3-kinase gamma (PI3Kgamma) and PI3Kdelta play an important role in the pathogenesis of asthma. Two key elements in allergic asthma are increased levels of eosinophils and IgE. Dual pharmacological inhibition of p110gamma and p110delta reduces asthma-associated eosinophilic lung infiltration and ameliorates disease symptoms, whereas the absence of enzymatic activity in p110gammaKOdeltaD910A mice increases IgE and basal eosinophil counts. This suggests that long-term inhibition of p110gamma and p110delta might exacerbate asthma. Here, we analysed mice genetically deficient for both catalytical subunits (p110gamma/delta-/-) and determined basal IgE and eosinophil levels and the immune response to ovalbumin-induced asthma. Serum concentrations of IgE, IL-5 and eosinophil numbers were significantly increased in p110gamma/delta-/- mice compared to single knock-out and wildtype mice. However, p110gamma/delta-/- mice were protected against OVA-induced infiltration of eosinophils, neutrophils, T and B cells into lung tissue and bronchoalveolar space. Moreover, p110gamma/delta-/- mice, but not single knock-out mice, showed a reduced bronchial hyperresponsiveness. We conclude that increased levels of eosinophils and IgE in p110gamma/delta-/- mice do not abolish the protective effect of p110gamma/delta-deficiency against OVA-induced allergic airway inflammation. |
