Dexmedetomidine attenuates acute lung injury induced by lipopolysaccharide in mouse through inhibition of MAPK pathway.

Abstract

Dexmedetomidine (Dex) is widely used for sedation in intensive care units and can be used as an adjunct to anesthetics. Previous studies have demonstrated that Dex has anti-inflammatory property. In this study, we aim to explore the potential therapeutic effects and mechanisms of Dex on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. To induce ALI, mice were intraperitoneally injected with LPS, while Dex was treated 1 h before LPS injection. The inflammation of lung tissues was evaluated by HE stain, and bronchoalveolar lavage fluid (BALF) was obtained after 6 h to measure protein concentrations. We also used an enzyme-linked immunosorbent assay to detect the secretion levels of proinflammatory cytokines in the serum. Western blotting method was adopted to observe changes in mitogen-activated protein kinases and downstream nuclear transcription factors. The results showed that pretreatment with Dex considerably reduced neutrophil infiltration and pulmonary edema, and significantly reduced protein concentrations in the BALF, as well as suppressed LPS-induced elevation of proinflammatory cytokines (TNF-α and IL-1β) in the serum. In addition, we observed that the molecular mechanism of Dex-mediated anti-inflammation is associated with decreasing phosphorylation of MKK4, MMK3/6, ERK1/2, p38MAPK, and JNK, and diminishing activation of Elk-1, c-Jun, and ATF-2. Dex could attenuate ALI induced by LPS in mice, and this effect may be mediated through the inhibition of MAPK pathway.

• Authors: Yingzhen Xu, Ruyi Zhang, Chunli Li, Xue Yin, Changjun Lv, Yaoqi Wang, Wenxiang Zhao, Xiuli Zhang
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 29 Issue 5 Pg. 462-71 (Oct 2015) ISSN: 1472-8206 [Electronic] England
• PMID: 26211495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Société Française de Pharmacologie et de Thérapeutique.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Inflammation Mediators
• Lipopolysaccharides
• Transcription Factors
• lipopolysaccharide, Escherichia coli O111 B4
• Dexmedetomidine
• Mitogen-Activated Protein Kinases

Topics

• Acute Lung Injury (chemically induced, enzymology, genetics, pathology, prevention & control)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Bronchoalveolar Lavage Fluid (chemistry)
• Cytokines (metabolism)
• Cytoprotection
• Dexmedetomidine (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Enzyme Activation
• Inflammation Mediators (metabolism)
• Lipopolysaccharides
• Lung (drug effects, enzymology, pathology)
• MAP Kinase Signaling System (drug effects)
• Male
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• Neutrophil Infiltration (drug effects)
• Phosphorylation
• Pulmonary Edema (chemically induced, enzymology, prevention & control)
• Time Factors
• Transcription Factors (genetics, metabolism)
• Transcription, Genetic (drug effects)