Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression.

Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE

Original Publication: Amsterdam ; New York : Elsevier Science, c2001-

Anti-Inflammatory Agents*/pharmacology ; Anti-Inflammatory Agents*/therapeutic use ; Salicylates*/pharmacology ; Salicylates*/therapeutic use; Acute Lung Injury/*drug therapy ; Lactose/*analogs & derivatives ; MAP Kinase Kinase Kinases/*antagonists & inhibitors ; NF-kappa B/*antagonists & inhibitors ; NLR Family, Pyrin Domain-Containing 3 Protein/*antagonists & inhibitors; Acute Lung Injury/metabolism ; Acute Lung Injury/pathology ; Animals ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoalveolar Lavage Fluid/cytology ; Cell Count ; Cytokines/blood ; Cytokines/metabolism ; Lactose/pharmacology ; Lactose/therapeutic use ; Lipopolysaccharides ; Lung/drug effects ; Lung/metabolism ; Lung/pathology ; MAP Kinase Kinase Kinases/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; NF-kappa B/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Peroxidase/metabolism ; Phosphorylation/drug effects ; RAW 264.7 Cells

Acute lung injury (ALI), characterized by pulmonary edema and inflammatory cell infiltration, is a common syndrome of acute hypoxemic respiratory failure. Methyl salicylate 2-O-β-d-lactoside (MSL), a natural derivative of salicylate extracted from Gaultheria yunnanensis (Franch.) Rehder, was reported to have potent anti-inflammatory effects on the progression of collagen or adjuvant-induced arthritis in vivo and in vitro. The aim of this study is to investigate the therapeutic effect of MSL on lipopolysaccharide (LPS)-induced acute lung injury and reveal underlying molecular mechanisms. Our results showed that MSL significantly ameliorated pulmonary edema and histological severities, and inhibited IL-6 and IL-1β production in LPS-induced ALI mice. MSL also reduced MPO activity in lung tissues and the number of inflammatory cells in BALF. Moreover, we found that MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation, as well as the expression of NLRP3 protein in lung tissues. Furthermore, MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation in Raw264.7 cells. In addition, MSL significantly inhibited nuclear translocation of NF-κB p65 in cells treated with LPS in vitro. Taken together, our results suggested that MSL exhibited a therapeutic effect on LPS-induced ALI by inhibiting TAK1/NF-κB phosphorylation and NLRP3 expression.
(Copyright © 2016 Elsevier B.V. All rights reserved.)

Keywords: Acute lung injury; Lipopolysaccharide; Methyl salicylate 2-O-β-d-lactoside; NF-κB; NLRP3; TAK1

0 (Anti-Inflammatory Agents)
0 (Cytokines)
0 (Lipopolysaccharides)
0 (NF-kappa B)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (Nlrp3 protein, mouse)
0 (Salicylates)
0 (methyl salicylate 2-O-lactoside)
EC 1.11.1.7 (Peroxidase)
EC 2.7.11.25 (MAP Kinase Kinase Kinases)
EC 2.7.11.25 (MAP kinase kinase kinase 7)
J2B2A4N98G (Lactose)

Date Created: 20160914 Date Completed: 20170515 Latest Revision: 20170515

20240829

10.1016/j.intimp.2016.08.041

27620503