ANGPTL4 silencing significantly mitigated allergic rhinitis-related symptoms, Treg/Th17 cell imbalance, and inflammatory cascades in mice by inactivating the Notch signaling pathway.
Does ANGPTL4 silencing alleviate inflammation and improve Treg/Th17 cell balance in an OVA-induced allergic rhinitis mouse model?
ANGPTL4 knockdown alleviates allergic rhinitis symptoms and inflammation in mice by improving Treg/Th17 balance via Notch signaling pathway suppression.
BACKGROUND: This study investigates the effect of angiopoietin-like 4 (ANGPTL4) on allergic rhinitis (AR) and explores the underlying mechanisms. METHODS: A mouse model of AR was generated through ovalbumin (OVA) challenge. The numbers of nasal rubbing and sneezing were counted and scored. Histological staining was conducted to analyze pathological alterations and inflammation in the mouse nasal mucosa. Inflammatory cytokines in serum and nasal lavage fluid (NALF) samples were analyzed using ELISA kits. Populations of regulatory T cells (Tregs) and Th17 cells in NALF or lymph nodes were analyzed using flow cytometry. Mice with AR were administered short hairpin (sh) RNAs targeting ANGPTL4. The effect of Notch pathway in AR severity was analyzed by gain- and loss-of-function assays. RESULTS: The consistent OVA challenge led to significant AR-like symptoms in mice, along with increased Notch signaling activation. Inhibiting this pathway using γ-secretase inhibitor (DAPT) markedly reduced the AR scores and alleviated inflammatory infiltration by improving Treg/Th17 cell balance. ANGPTL4 silencing significantly mitigated AR-related symptoms, Treg/Th17 cell imbalance, and inflammatory cascades in mice by inactivating the Notch signaling pathway. However, these alleviating effects of ANGPTL4 silencing on mice were negated by the administration of valproic acid, an agonist of the Notch signaling. CONCLUSION: This paper provides evidence that the ANGPTL4 knockdown shows significant therapeutic effects on AR by improving the Treg/Th17 cell balancing, effects achieved, at least in part, by blocking the Notch signaling pathway.
Han et al. (Tue,) conducted a other in Allergic rhinitis (mouse model). ANGPTL4-shRNA vs. Empty virus control was evaluated on Allergic rhinitis symptom severity (nasal rubbing and sneezing). ANGPTL4 silencing significantly mitigated allergic rhinitis-related symptoms, Treg/Th17 cell imbalance, and inflammatory cascades in mice by inactivating the Notch signaling pathway.