Propofol Inhibits HIF-1α/NLRP3 Signaling Pathway and Mast Cell Activation to Ameliorate Airway Inflammation in Allergic Asthma.

Abstract

BACKGROUND: The objective was to assess the effects of propofol on ovalbumin (OVA)-induced asthma in a mouse model and the efficacy of propofol in stabilizing mast cells and inhibiting the production of inflammatory mediators. METHODS: Animal model of asthma induced by OVA was employed to evaluate the effect of propofol. Tissues from the lungs were retrieved for HE staining. The levels of IgE, IFN-γ, MPO, and so on was deteced. Bone marrow mast cells (BMMCs) were isolated to examine the suppressive action of propofol on the degranulation. RESULTS: Propofol significantly reduced airway hyperresponsiveness and IgE, Th2 cytokines, and inflammatory cytokines in OVA-induced asthma model. Inhibited BMMCs degranulation and the production of inflammatory cytokines. Additionally, propofol inhibited the expression of HIF-1α and NLRP3 in asthma models. Overexpression HIF-1α in BMMCs reverses the effect of propofol. NLRP3 inhibition attenuates allergic asthma in DNP-HSA-treated DMMCs with or without overexpression HIF-1α. In terms of the mechanism, propofol interacts with HIF-1α directly, thereby disrupting HIF-1α-NLRP3 interaction and attenuating allergic asthma. CONCLUSION: Propofol markedly improved OVA-induced asthma and inhibited mast cell degranulation by binding competitively to HIF-1α, thereby disrupting the HIF-1α-NLRP3 interaction and attenuating allergic asthma.