LPS-induced lung inflammation is linked to increased epithelial permeability: role of MLCK

• Published in: The European respiratory journal Vol. 25; no. 5; pp. 789 - 796
• Main Authors: Eutamene, H, Theodorou, V, Schmidlin, F, Tondereau, V, Garcia-Villar, R, Salvador-Cartier, C, Chovet, M, Bertrand, C, Bueno, L
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01.05.2005; Maney; European Respiratory Society
• Subjects: Animals; Azepines - pharmacology; Biological and medical sciences; Cells, Cultured; Disease Models, Animal; Enzyme Inhibitors - pharmacology; Humans; Life Sciences; Lipopolysaccharides; Lung - enzymology; Male; Medical sciences; Myosin-Light-Chain Kinase - drug effects; Myosin-Light-Chain Kinase - metabolism; Naphthalenes - pharmacology; Permeability; Peroxidase - metabolism; Pneumology; Pneumonia - chemically induced; Pneumonia - enzymology; Rats; Rats, Wistar; Reference Values; Respiratory Mucosa - drug effects; Respiratory Mucosa - enzymology; Enzyme; Transferases; Lung; Lipopolysaccharide; Inflammation; Permeability; Airway epithelium; Epithelium; myosin light chain kinase; Myosin-light-chain kinase
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.05.00064704

The respiratory system is directly exposed to low levels of lipopolysaccharide (LPS), present as a contaminant on airborne particles. In cystic fibrosis, the prevailing data identify structural changes of the airway epithelium, as well as tight junction dilatation. This study was aimed at determining the contribution of myosin light chain kinase to maintaining airway epithelium barrier integrity in the lung inflammatory response to LPS in rats. The effects of the selective myosin light chain kinase inhibitor, 5-iodonaphthalene-1-sulphonyl-homopiperazine (ML-7), were evaluated: 1) on pulmonary inflammation and airway epithelium barrier permeability alterations induced by intra-tracheal LPS from Pseudomonas aeruginosa; and 2) on levels of the phosphorylated form of the myosin light chain, which is increased in a human airway epithelial cell line (NCI-H292) and tracheal tissue after LPS exposure. The results show that LPS increased airway epithelium barrier paracellular permeability and lung inflammation, and that pre-treatment with ML-7 inhibited both effects. This effect of ML-7 was associated with the inhibition of phosphorylated myosin light chain in both NCI-H292 cells and tracheal tissue. The data, obtained using in vivo and in vitro approaches, demonstrate a key role for myosin light chain kinase in lung inflammation, and suggest that myosin light chain kinase could be a potential target for novel drugs intended for relief of lung injury.