Inhibitor of γ-secretase alleviates middle ear inflammation by regulating Th2 response in OVA-mediated allergic OME in vivo.

In this study, we aimed to investigate the role of Notch signaling pathway in the ovalbumin (OVA)-mediated allergic OME in vivo. OVA-induced OME rats were treated with a control vehicle or a γ-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppressing the Notch signaling. We studied the effect of Notch signaling pathway in OME model, including histopathological assessment, the expression of Th1 cytokines (IFN-γ), Th2 cytokines (IL-4, IL-5), key transcription factors (T-bet, GATA-3) by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, the level of Notch ligand (Jagged1) and the downstream target gene Hes1 were also evaluated by qRT-PCR and immunofluorescent staining. We observed that the production of Th2 cytokines was increased, the level of Th1 cytokines was decreased in OME experimental model. Likewise, Th2-cytokine(IL-4)level was reduced, but the level of Th1 cytokines(IFN-γ) was no changes. Additionally, administration of DAPT induced a decrease in the expression of GATA-3 mRNA, however, no influence on T-bet mRNA production. These results suggest that there is an imbalance with Th1/Th2 in OVA-mediated allergic OME. DAPT treatment can block the Notch signaling pathway and relieve the middle ear inflammation through modulating the level of Th2 responses in OVA-induced allergic OME. PMID: 31515081 [PubMed - as supplied by publisher]
Source: Immunobiology - Category: Allergy & Immunology Authors: Tags: Immunobiology Source Type: research