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

H Eutamène, V Theodorou, F Schmidlin… - European …, 2005 - Eur Respiratory Soc
H Eutamène, V Theodorou, F Schmidlin, V Tondereau, R Garcia-Villar, C Salvador-Cartier…
European Respiratory Journal, 2005Eur Respiratory Soc
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 …
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.
European Respiratory Society