Lipoxin A4 ameliorates renal ischaemia-reperfusion-induced acute lung injury in rats.

Abstract

Lipoxin A4 (LA4), a bioactive product of arachidonic acid, has been shown to exert strong anti-inflammatory activity. By contrast, the anti-inflammatory action of LA4 in a renal ischaemia-reperfusion (RIR)-mediated acute lung inflammation (ALI) model and the potential pathogenesis of the condition is still unclear. The aim of the current research was to investigate the effect of LA4 on RIR-induced ALI. The rat ALI model was induced by RIR. LA4 was injected via the tail vein immediately after RIR. The results indicate that LA4 markedly inhibits inflammatory cells infiltration, attenuates myeloperoxidase activity, and reduces the concentration of inflammatory mediators and Toll-like receptor 4 (TLR4) in RIR-induced ALI. Furthermore, LA4 suppressed nuclear factor kappa B (NF-κB) p65 and mitogen-activated protein kinase (MAPK) activation. The protective effect of LA4 in RIR-stimulated ALI was reversed by BOC-2 (an antagonist of the LA4 receptor). These results indicate that LA4 exerts powerful anti-inflammatory functions in RIR-induced ALI by attenuating TLR4 expression via MAPK and NF-κB signalling. Accordingly, LA4 might be an underlying treatment drug for RIR-induced ALI.

• Authors: Zhaohui Liu, Min Qu, Qiang Yang, Yulin Chang
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 46 Issue 1 Pg. 65-74 (01 2019) ISSN: 1440-1681 [Electronic] Australia
• PMID: 30118542 (Publication Type: Journal Article)
• Copyright: © 2018 John Wiley & Sons Australia, Ltd.

Chemical References

• HMGB1 Protein
• Inflammation Mediators
• Lipoxins
• NF-kappa B
• Toll-Like Receptor 4
• lipoxin A4
• Peroxidase
• Mitogen-Activated Protein Kinases

Topics

• Acute Lung Injury (drug therapy, economics, metabolism, pathology)
• Animals
• Bronchoalveolar Lavage Fluid
• Cytoprotection (drug effects)
• Gene Expression Regulation (drug effects)
• HMGB1 Protein (metabolism)
• Inflammation Mediators (metabolism)
• Kidney (blood supply)
• Lipoxins (pharmacology, therapeutic use)
• Male
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Peroxidase (metabolism)
• Phosphorylation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (complications)
• Toll-Like Receptor 4 (metabolism)