Hypoxia inducible factor-2α knockout macrophages alleviate the renal ischemia-reperfusion injury via regulating the expression of inflammatory cytokines

Abstract

Objective To investigate the protective effect of hypoxia inducible factor-2α (HIF-2α) knockout macrophages to renal ischemia-reperfusion injury through regulating the expression of inflammatory cytokines. Methods The HIF-2α+ /+ and HIF-2α-/-mice were randomly divided into the sham operation group (n=20) and renal IR group (n=20) . The survival time of mice was observed. Mice were sacrificed 24 h after renal reperfusion to obtain blood and renal samples. The expressions of blood urea nitrogen (BUN), creatinine (Cr) in serum and the inflammatory cytokines encoding interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in serum as well as renal tissues were measured. In addition, the histomorphological changes were analyzed via hematoxylin and eosin (HE) staining. Macrophages derived from bone marrow of HIF-2α+ /+ and HIF-2α-/- mice were divided into normoxic group and hypoxic group. The levels in cell culture supernatants of IL-1β, IL-6, IL-10, TNF-α and IFN-γ were examined by enzyme linked immunosorbent assay (ELISA). Results Compared with HIF-2α+ /+ + IR group, mice in HIF-2α-/-+ IR group had significantly longer survival time (P 0.05) . Compared with HIF-2α+ /+ + hypoxic group, bone marrow-derived macrophages (BMDMs) obtained from HIF-2α-/-mice under hypoxic had significantly higher levels of TNF-α and IL-6 (t=12.196, 8.498, P 0.05) . Conclusion Knockout of HIF-2α in macrophages can reduce the secretion of proinflammatory cytokines and increase anti-inflammatory cytokines to protect against renal ischemia-reperfusion injury. Key words: Hypoxia inducible factor-2α; Macrophage; Kidney; Ischemia-reperfusion injury.