Abstract
Background and objective Lung inflammation is a pivotal event in the pathogenesis of acute lung injury. Heme oxygenase-1 (HO-1) is a key antioxidant enzyme which could be induced by Kaempferol (KPR) and exerts anti-inflammatory effects. However, the molecular mechanisms of KPR-mediated HO-1 expression and its effects on inflammatory responses remain unknown in human pulmonary alveolar epithelial cells (HPAEpiCs). The aim of this study was to verify the relationship between HO-1 expression and KPR treatment in both in vitro and in vivo models. Methods: The HO-1 expression was determined by Western blotting, real time-PCR, and promoter analyses. The signaling molecules were investigated by pretreatment with respective pharmacological inhibitors or transfection with siRNAs. The interaction between HO-1 promoter and transcription factors was determined by ChIP assay. Finally, the effect of KPR on HPAEpiCs migration and leukocyte count in BAL fluid and HO-1 expression induced by LPS was determined by cell migration assay, cell counting, and Western blot. Results: We observed that KPR induced HO-1 protein and mRNA expression through aSrc-dependent NOX/ROS/p38 or Pyk2/PKCα/JNK pathway. In addition, up-regulation of HO-1 by KPR suppressed the ICAM-1expression and monocyte adhesion on LPS-challenged HPAEpiCs. These results were further confirmed by an animal study, indicating that LPS-induced ICAM-1 expression and leukocyte recruitment was attenuated by pretreatment with KPR through up-regulation of HO-1. Conclusions: KPR could be a potential intervention against inflammation by up-regulating HO-1 expression and down-regulating ICAM-1 expression in HPAEpiCs.
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