Inhalation of Salvianolic Acid B Prevents Fine Particulate Matter-Induced Acute Airway Inflammation and Oxidative Stress by Downregulating the LTR4/MyD88/NLRP3 Pathway.

Abstract

Air pollution is a serious threat to human health. Inhaled fine particulate matter (PM2.5) can cause inflammation and oxidative stress in the airway; however, the mechanisms responsible for this effect have yet to be elucidated and there are no specific drugs that can prevent and treat this condition. In the present study, we investigated the effects and mechanisms underlying the inhalation of salvianolic acid B (SalB) on PM2.5-induced airway inflammation and oxidative stress. We used a PM2.5-induced mouse model of airway inflammation and oxidative stress, along with a human epithelial cell model, to study the action and mechanisms of SalB by histopathology, real-time PCR, enzyme-linked immunosorbent assays, flow cytometry, and western blotting. SalB treatment markedly inhibited the PM2.5-induced increase in the number of neutrophils and macrophages in bronchoalveolar lavage fluid, improved the infiltration of inflammatory cells in lung tissue, and reduced injury in the alveolar septum. Furthermore, SalB reduced the mRNA and protein levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, keratinocyte (KC), and transforming growth factor- (TGF-) β1 in lung tissues and the protein levels of IL-1β, TNF-α, IL-8, IL-6, and TGF-β1 in human epithelial cells. SalB treatment also significantly prevented the reduction of levels of superoxide dismutase, catalase, glutathione, and glutathione peroxidase in lung tissue and reduced the levels of reactive oxygen species in human epithelial cells induced by PM2.5. Furthermore, SalB and the myeloid differentiation primary response 88 (MyD88) inhibitor ST2825 inhibited the expression levels of toll-like receptor 4 (TLR4), MyD88, tumor necrosis factor receptor associated factor 6 (TRAF-6), and NOD-like receptor protein 3 (NLRP3), as well as the phosphorylation of downstream Erk1/2 and P38 in lung tissue and epithelial cells. SalB protects against PM2.5-induced airway inflammation and oxidative stress in a manner that is associated with the inhibition of the TLR4/MyD88/TRAF-6/NLRP3 pathway and downstream signals ERK1/2 and P38.