Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway.

Autor:	Nie Y; Department of Pediatrics, Wuhan No.1 Hospital, Wuhan City, China., Yang B; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan City, China., Hu J; Department of Pediatrics, Wuhan No.1 Hospital, Wuhan City, China., Zhang L; Department of Pediatrics, Wuhan No.1 Hospital, Wuhan City, China., Ma Z; Department of Respiratory Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang City, China; zmma9802@163.com.
Jazyk:	angličtina
Zdroj:	Allergologia et immunopathologia [Allergol Immunopathol (Madr)] 2021 Nov 04; Vol. 49 (6), pp. 73-79. Date of Electronic Publication: 2021 Nov 04 (Print Publication: 2021).
DOI:	10.15586/aei.v49i6.499
Abstrakt:	Allergic asthma is a heterogeneous inflammatory disorder triggered by inhaled allergens, leading to airflow obstruction, bronchial inflammation, and airway hyperresponsiveness (AHR). T helper (Th) 2 cell-mediated immune response and airway inflammation are the key features of allergic asthma. Bruceine D (BD) is a bioactive compound extracted from the seeds of Brucea javanica . The present study aimed to investigate the effects of increased doses of BD on AHR, secretion of Th1-/Th2-associated cytokines, and inflammatory cell infiltration in ovalbumin (OVA)-induced allergic asthma mice. The results showed that BD reduced OVA-induced inflammatory cell infiltration and bronchial hyperresponsiveness into the peribronchial tissues and perivascular areas. Mice treated with BD also showed significantly decreased expressions of Th2-associated cytokines (i.e., interleukin (IL)-4, IL-5, and IL-13) and elevated production of Th1-associated cytokines (i.e., interferon gamma and IL-2) following OVA stimulation. BD treatment dose-dependently inhibited OVA-induced accumulation of inflammatory cells in asthmatic mice. Further analysis revealed that OVA exposure upregulated pulmonary expressions of NOTCH signaling receptors, a group of transmembrane proteins that communicate signals upon binding to transmembrane ligands expressed on adjacent cells, while BD treatment significantly abolished OVA-induced activation of the NOTCH pathway. In conclusion, BD protected mice against OVA-induced allergic asthma by reducing AHR and restoring the Th1/Th2 balance through the NOTCH signaling pathway. Our findings highlighted the potential of BD as a therapeutic agent for allergic asthma. Competing Interests: The authors state that there are no conflicts of interest to disclose.
Databáze:	MEDLINE
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