Anti-inflammatory effect of pre-elafin in lipopolysaccharide-induced acute lung inflammation.

Abstract

The aim of the present study was to evaluate the anti-inflammatory activity of pre-elafin, an elastase-specific inhibitor, in lipopolysaccharide (LPS)-induced acute lung inflammation. C57BL/6 mice were pre-treated intranasally with recombinant human pre-elafin or vehicle only. One hour later, they were instilled intranasally with LPS (2 microg/mouse). Animals were sacrificed 6 hours after LPS instillation and bronchoalveolar lavage (BAL) was performed with three 1-ml aliquots of saline. LPS induced a lung inflammation characterised by a 100-fold increase in BAL neutrophils compared to control animals (265.8 +/- 54.5 x 10(3) and 2.4 +/- 1.3 x 10(3) neutrophils/ml, respectively). Pre-elafin dose-dependently reduced the neutrophil influx in the lung alveolar spaces by up to 84%. No elastase activity was detectable in all BAL fluids tested. Pre-elafin also reduced significantly LPS-induced gelatinase activity, as shown by zymography, and BAL macrophage inflammatory protein-2 (MIP-2) and KC levels, two potent neutrophil attractants and activators. Moreover, pre-elafin also significantly reduced mRNA levels of the three members of the IL-1 ligand family, namely IL-1alpha, IL-1beta and IL-1 receptor antagonist (IL-1Ra), type II IL-1 receptor, and TNFalpha as assessed in whole lung tissue by RNase protection assay. Thus, pre-elafin may be considered as a potent anti-inflammatory mediator.

• Authors: Eric Vachon, Yves Bourbonnais, Colin D Bingle, Sarah J Rowe, Marie France Janelle, Guy M Tremblay
• Journal: Biological chemistry (Biol Chem) 2002 Jul-Aug Vol. 383 Issue 7-8 Pg. 1249-56 ISSN: 1431-6730 [Print] Germany
• PMID: 12437112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Enzyme Precursors
• Lipopolysaccharides
• Proteinase Inhibitory Proteins, Secretory
• Proteins
• Recombinant Fusion Proteins
• Pancreatic Elastase
• Gelatinases

Topics

• Acute Disease
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Bronchoalveolar Lavage Fluid (cytology)
• Cytokines (drug effects)
• Enzyme Precursors (pharmacology)
• Female
• Gelatinases (drug effects)
• Humans
• Lipopolysaccharides (pharmacology)
• Mice
• Mice, Inbred C57BL
• Neutrophils (drug effects)
• Pancreatic Elastase (drug effects)
• Pneumonia (chemically induced, drug therapy, immunology)
• Proteinase Inhibitory Proteins, Secretory
• Proteins (pharmacology)
• Recombinant Fusion Proteins (pharmacology)