Abstract: Objective To investigate the effect of hypoxia on the expression of IL-1β in macrophages. Methods RAW264.7 cells were treated with normoxia (21% O2), hypoxia (2% O2), normoxia (21% O2) following treatment with LPS and hypoxia (2% O2) following treatment with LPS. RT-qPCR was used to detect the mRNA expression of Vegf, Nlrp3 and Il1b. Western blot was used to detect the protein expression of HIF-1α, NLRP3, caspase-1, cleaved caspase-1, Pro-IL-1β and IL-1β. The peritoneal macrophages of Vhlfl/fl/Apoe-/- mice and VhlΔMac/Apoe-/- mice were treated with or without LPS. RT-qPCR was used to detect the mRNA expression of Vhl, Nlrp3, Il1b and Il6. Results Compared with normoxia, hypoxia only significantly increased the mRNA levels of Vegf, Nlrp3 and Il1b in RAW264.7 (P<0.01). Hypoxia augmented the mRNA and protein levels of NLRP3 and IL-1β in RAW264.7 induced with LPS comparing with normoxia (P<0.01). Hypoxia had no effects on the activation of caspase-1 and the subsequent maturation of Pro-IL-1β induced with LPS in RAW264.7. Compared with Vhlfl/fl/Apoe-/- peritoneal macrophages, VhlΔMac/Apoe-/- peritoneal macrophages showed significantly increased mRNA levels of Nlrp3, Il1b and Il6 induced with LPS (P<0.05). Conclusions Hypoxia amplifies lipopolysaccharide-induced IL-1β expression in macrophages.

Key words: hypoxia, hypoxia inducible factor, macrophage, IL-1β