Tanshinone IIA–Induced Attenuation of Lung Injury in Endotoxemic Mice Is Associated with Reduction of Hypoxia-Inducible Factor 1α Expression

• DOI: 10.1165/rcmb.2011-0113oc
• Publication Date: 2011-05-27T04:50:16Z
• Authors: Min Xu; Fale Cao; Lili Liu; Bo Zhang; Yanxia Wang; Haiying Dong; Yan Cui; Mingqing Dong; Dunquan Xu; Yi Liu; Pengtao Zhao; Wen Niu; Zhichao Li
• Keywords: Hypoxia; Hypoxia-Inducible Factors

Inhibiting hypoxia-inducible factor (HIF)-1α activity has been proposed as a novel therapeutic target in LPS-induced sepsis syndrome. We have reported that tanshinone IIA (TIIA) can reduce lethality and lung injury mice, but the precise mechanisms not fully described. Therefore, present study investigated whether protective effect of TIIA was related to inhibition HIF-1α expression what accounted for it. This showed pretreatment improved biochemical cellular changes reduced production inflammatory cytokines. Pretreatment with decreased vivo vitro. did affect mRNA level inhibited protein translation by PI3K/AKT MAPK pathways translational regulators, such p70S6K1, S6 ribosomal protein, 4E-BP1, eIF4E, promoted degradation via proteasomal pathway LPS-stimulated macrophages. These observations partially explain antiinflammatory effects TIIA, which provides scientific basis its application treatment acute injury/acute respiratory distress syndrome or sepsis.