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

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.