Contribution of CFTR to alveolar fluid clearance by lipoxin A4 via PI3K/Akt pathway in LPS-induced acute lung injury.

Abstract

The lipoxins are the first proresolution mediators to be recognized and described as the endogenous "braking signals" for inflammation. We evaluated the anti-inflammatory and proresolution bioactions of lipoxin A4 in our lipopolysaccharide (LPS-)induced lung injury model. We demonstrated that lipoxin A4 significantly improved histology of rat lungs and inhibited IL-6 and TNF- α in LPS-induced lung injury. In addition, lipoxin A4 increased alveolar fluid clearance (AFC) and the effect of lipoxin A4 on AFC was abolished by CFTRinh-172 (a specific inhibitor of CFTR). Moreover, lipoxin A4 could increase cystic fibrosis transmembrane conductance regulator (CFTR) protein expression in vitro and in vivo. In rat primary alveolar type II (ATII) cells, LPS decreased CFTR protein expression via activation of PI3K/Akt, and lipoxin A4 suppressed LPS-stimulated phosphorylation of Akt. These results showed that lipoxin A4 enhanced CFTR protein expression and increased AFC via PI3K/Akt pathway. Thus, lipoxin A4 may provide a potential therapeutic approach for acute lung injury.

• Authors: Yi Yang, Yang Cheng, Qing-Quan Lian, Li Yang, Wei Qi, De-Rong Wu, Xia Zheng, Yong-Jian Liu, Wen-Juan Li, Sheng-Wei Jin, Fang Gao Smith
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2013 Pg. 862628 ( 2013) ISSN: 1466-1861 [Electronic] United States
• PMID: 23766562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Interleukin-6
• Lipopolysaccharides
• Lipoxins
• Tumor Necrosis Factor-alpha
• lipoxin A4
• Cystic Fibrosis Transmembrane Conductance Regulator
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Acute Lung Injury (chemically induced, drug therapy, metabolism)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Blotting, Western
• Cells, Cultured
• Cystic Fibrosis Transmembrane Conductance Regulator (genetics, metabolism)
• Fluorescent Antibody Technique
• Immunohistochemistry
• Interleukin-6 (metabolism)
• Lipopolysaccharides (toxicity)
• Lipoxins (therapeutic use)
• Male
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)