Abstract
Previous studies have shown that cigarette smoke-induced inflammation is a key driver of chronic obstructive pulmonary disease (COPD) progression. Sodium butyrate (NaB), a short-chain fatty acid that can be endogenously produced or exogenously supplemented, has been reported to exhibit anti-inflammatory effects. This study investigated the therapeutic effects and mechanisms of NaB in cigarette smoke extract (CSE)-induced inflammation. Through network pharmacology analysis, von Willebrand factor (VWF) was identified as a potential key target of NaB in the regulation of COPD. qRT-PCR and Western blot analysis showed that CSE significantly upregulated VWF expression in human umbilical vein endothelial cells (HUVECs), while NaB treatment markedly suppressed this upregulation. Using small interfering RNA (si-VWF), we knocked down VWF expression in HUVECs and co-cultured these cells with THP-1 cells in CSE-containing medium. ELISA, qRT-PCR, and Western blot analysis revealed that CSE enhanced the inflammatory response and activation of the PI3K-AKT signaling pathway in the THP-1. However, VWF knockdown reversed these effects of CSE. Furthermore, NaB pre-treatment of HUVECs significantly inhibited the inflammatory response and PI3K-AKT signaling activation in THP-1 cells, whereas VWF overexpression partially reversed the inhibitory effects of NaB. This study elucidated the critical regulatory role of VWF in CSE-induced endothelial cell-macrophage crosstalk and demonstrated that NaB suppresses CSE-induced VWF upregulation in HUVECs, thereby mitigating macrophage inflammation. Our findings reveal a novel mechanism by which NaB inhibits CSE-induced inflammation and highlight the therapeutic potential of NaB in COPD.
Supplementary Information:
The online version contains supplementary material available at 10.1186/s12931-025-03338-y.
Keywords:
Cigarette smoke extract; Endothelial cells; Macrophages; Sodium butyrate; VWF.