p38MAPK inhibition attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway

• Published in: European journal of pharmacology Vol. 584; no. 1; p. 159
• Main Authors: Liu, Su, Feng, Guang, Wang, Guang-Lei, Liu, Gong-Jian
• Format: Journal Article
• Language: English
• Published: Netherlands 14.04.2008
• Subjects: Animals; Bronchoalveolar Lavage Fluid - chemistry; Cytokines - metabolism; Disease Models, Animal; Enzyme Activation; I-kappa B Proteins - metabolism; Imidazoles - administration & dosage; Imidazoles - pharmacology; Inflammation Mediators - metabolism; Injections, Intravenous; Interleukin-6 - metabolism; Lipopolysaccharides; Lung - drug effects; Lung - enzymology; Lung - metabolism; Lung - pathology; Male; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Organ Size; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - pharmacology; Pyridines - administration & dosage; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome, Adult - chemically induced; Respiratory Distress Syndrome, Adult - drug therapy; Respiratory Distress Syndrome, Adult - metabolism; Respiratory Distress Syndrome, Adult - pathology; Signal Transduction - drug effects; Time Factors; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0014-2999
• DOI: 10.1016/j.ejphar.2008.02.009

The pathogenesis of acute lung injury/acute respiratory distress syndrome (ARDS) is complex and involves multiple signal transduction processes. It is believed that p38MAPK (mitogen-activated protein kinase) is one of the most kinases in inflammatory signaling. At present study, we demonstrated the role of p38MAPK in lipopolysaccharide (LPS)-induced acute lung injury with pharmacologic p38MAPK inhibition by SB203580. SB203580, p38MAPK specific inhibitor, was injected (10 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). The hematoxylin-eosin staining of lung tissues showed that p38MAPK inhibition significantly attenuated the pulmonary inflammatory responses induced by LPS. Moreover, SB203580 can also inhibit the inflammatory cytokine release, and reduce the mortality rate of LPS-induced acute lung injury. Further, western blot analysis that showed SB203580 administration can inhibit the activation of NF-kappaB, which was associated with the inhibition of IkappaBalpha degradation in cytoplasm. These data suggest that p38MAPK signaling may be involved in the activation of NF-kappaB, and activation of p38MAPK signaling may be one of the mechanisms of acute lung injury.