title: p38MAPK inhibition attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway.
abstract: 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.
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, People's Republic of China.
authors.forename: Su
authors.initials: S
authors.lastname: Liu
authors.forename: Guang
authors.initials: G
authors.lastname: Feng
authors.forename: Guang-Lei
authors.initials: GL
authors.lastname: Wang
authors.forename: Gong-Jian
authors.initials: GJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D020672:I-kappa B Proteins / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009929:Organ Size; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016207:Cytokines; D020672:I-kappa B Proteins; D007093:Imidazoles; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C482199:lipopolysaccharide, E coli O55-B5; D000072000:NF-KappaB Inhibitor alpha; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580