title: Endotoxin tlerance inhibits lipopolysaccharide-initiated acute pulmonary inflammation and lung injury in rats by the mechanism of nuclear factor-kappaB.
abstract: In this study, the effect of endotoxin tolerance on lipopolysaccharide (LPS)-initiated pulmonary inflammation, the local production of tumour necrosis factor-alpha (TNF-alpha) and the cytokine-induced neutrophil attractant (CINC), as well as the activation of nuclear factor-kappaB (NF-kappaB) and its subunit composition, were examined in vivo. Endotoxin tolerance was reproduced by four consecutive daily intraperitoneal injections of 0.6 mg/kg of Escherichia coli 055:B5 LPS. Compared with control rats, endotoxin-tolerant rats failed to increase the permeability of pulmonary microvascular or recruit neutrophil to lung tissue upon restimulation with 6 mg/kg of LPSs. Pretreatment with LPSs inhibited the protein level of TNF-alpha in bronchoalveolar lavage fluid (BALF) and mRNA expression of CINC in lung tissue in response to subsequent LPS stimulation. These changes were accompanied by the suppression of activation of NF-kappaB, including the low level of total amount of DNA-binding activity and high percentage of non-transactive p50 homodimers. These data demonstrate that endotoxin tolerance can alleviate the LPS-induced acute neutrophilic pulmonary inflammation in rats and can inhibit the proinflammatory cytokines in lung and suggest that endotoxin tolerance might result from the unresponsiveness of NF-kappaB and persistent high percentage of p50 homodimers. Therefore, the phenomenon of endotoxin tolerance might be used as a strategy for the prevention or treatment of LPS-associated acute respiratory distress syndrome in which excessive or dysregulated inflammation leads to acute lung injury.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. jmqu64@yahoo.com.cn
authors.forename: J
authors.initials: J
authors.lastname: Qu
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: Z
authors.initials: Z
authors.lastname: Ou
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Chen
mesh_terms: D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability; D019743:Chemokines, CXC / Q000235:genetics; D004361:Drug Tolerance; D019446:Endotoxemia / Q000150:complications; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D011014:Pneumonia / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha