title: Bone Marrow Mesenchymal Stem Cells Suppress Acute Lung Injury Induced by Lipopolysaccharide Through Inhibiting the TLR2, 4/NF-κB Pathway in Rats with Multiple Trauma.
abstract: Multiple trauma normally leads to acute lung injury (ALI) and other multiple organ dysfunction syndrome (MODS). Finding effective treatments for ALI remains a medical as well as socioeconomic challenge. Several studies show that bone marrow mesenchymal stem cells (BMSCs) have the potent anti-inflammation activity and transfusion of BMSCs can effectively inhibit inflammatory and autoimmune diseases.
  
  
  
  In this study, we investigated the TLR2, 4/NF-κB signaling pathway to determine the therapeutic value of BMSCs on lipopolysaccharide (LPS)-induced ALI. To investigate the immunosuppression effects of BMSCs, rats subjected to multiple trauma were administrated with LPS to induce ALI and then treated with BMSCs. The histology of the lung was examined. Serum levels of the pro-inflammatory factors TNFα, interleukin (IL)-6, and IL-1β, as well as anti-inflammatory factor IL-10 were measured at 3, 6, 12, and 24 h after the treatment. Moreover, expressions of TLR2 and TLR4 at the mRNA and protein levels, as well as phosphorylation of p65 in the lungs, were assessed at these time points.
  
  
  
  We found that BMSCs reduced inflammatory injury, inhibited LPS-induced upregulation of TLR2 and TLR4 expression at the mRNA and protein levels, and compromised p65 phosphorylation. In addition, infusion of BMSCs also downregulated the abundance of pro-inflammatory TNFα, IL-6, and IL-1β and upregulated the abundance of anti-inflammatory IL-10 levels in the serum.
  
  
  
  Our results suggest that BMSCs suppress the inflammatory reactions through inhibition of the TLR2, 4 mediated NF-κB signal pathway, which hints that BMSCs can potentially be used to treat ALI in multiple trauma.
authors.affiliation: *Department of Traumatology Medicine, The First Affiliated Hospital of Wenzhou Medical University †School of Pharmaceutical Sciences, Wenzhou Medical University ‡Department of Intensive Care Unit §Department of Cardiothoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
authors.forename: Dequan
authors.initials: D
authors.lastname: Li
authors.forename: Xuebo
authors.initials: X
authors.lastname: Pan
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Chuang
authors.initials: C
authors.lastname: Chi
authors.forename: Guangyu
authors.initials: G
authors.lastname: Wu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Shiyao
authors.initials: S
authors.lastname: Liao
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Jihong
authors.initials: J
authors.lastname: Ma
authors.forename: Jingye
authors.initials: J
authors.lastname: Pan
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D009102:Multiple Organ Failure / Q000209:etiology / Q000628:therapy; D009104:Multiple Trauma / Q000473:pathology; D051381:Rats; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha