ANXA3 regulates HIF1α-induced NLRP3 inflammasome activity and promotes LPS-induced inflammatory response in bronchial epithelial cells

Introduction: Childhood asthma is one of the most common pediatric diseases, and its incidence is increasing. Annexin A3 (ANXA3) is a member of the Annexin family, a well-known polygenic family of membrane binding proteins. Bioinformation analysis showed that ANXA3 was highly expressed in asthmatic patients, suggesting the effects of ANXA3 on asthma, whereas the mechanism is still unclear.

Methods: A inflammatory response model of bronchial epithelial BEAS-2B cells induced by LPS was constructed. Immunoblot and quantitative PCR assays were performed to detect the expression levels of ANXA3 in control or LPS-induced BEAS-2B cells. MTT, flow cytometry (FCM), and Immunoblot assays were respectively conducted to detect the effects of ANXA3 on survival and apoptosis of LPS-induced BEAS-2B cells. qPCR and ELISA assays were performed to detect the expression of TNF-α, IL-6, and IL-8. Additionally, Immunoblot assays were performed to detect the effects of ANXA3 on HIF1α and NLRP3 inflammasome in BEAS-2B cells.

Results: We found ANXA3 was overexpressed in LPS-induced BEAS-2B cells. ANXA3 ablation promoted the survival of LPS-induced BEAS-2B cells and suppressed the inflammatory response of LPS-induced BEAS-2B cells. Importantly, we noticed ANXA3 inhibited HIF1α-induced NLRP3 inflammasome activity, and increasing the expression of HIF-α rescued the effects of ANXA3 depletion on asthma.

Conclusion: ANXA3 enhanced LPS-triggered inflammation of human bronchial epithelial cells by regulating hypoxia-inducible factor-1α (HIF1α)-mediated NLRP3 inflammasome activation, and thought ANXA3 as a promising molecular target for acute asthma treatment.

Annexin A3 (ANXA3); Acute asthma; Inflammatory response; NLRP3 inflammasome; Hypoxia-inducible factor-1α (HIF1α)

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