title: Acid-induced lung injury: role of nuclear factor-kappaB.
abstract: BACKGROUND
  Aspiration of acidic gastric contents leads to acute lung injury and is still one of the most common clinical events associated with acute lung injury. This study was performed to assess acid-induced lung inflammation in vitro and in vivo with respect to the time pattern of activated transcription factor nuclear factor-kappaB (NF-kappaB) and proinflammatory molecules.
  
  
  METHODS
  L2 cells (alveolar epithelial cells) were exposed for various periods to a medium with a pH of 6. In the in vivo model, 1 ml/kg of 0.1 n acidic solution was instilled into the lungs of rats. NF-kappaB binding activity and expression pattern of inflammatory mediators were determined. Blocking studies were performed with the NF-kappaB inhibitor pyrrolidine dithiocarbamate.
  
  
  RESULTS
  In vitro NF-kappaB binding activity showed a biphasic expression pattern with a first peak at 1 h and a second one at 6-8 h. In acid-injured rat lungs, NF-kappaB binding activity was confirmed in a biphasic manner with a first increase at 0.5-2 h (608 +/- 93% and 500 +/- 15%, respectively, P < 0.05) and a second peak at 8 h (697 +/- 35% increase, P < 0.005). Whole lung mRNA for macrophage inflammatory protein-1beta and macrophage inflammatory protein-2 showed a similar expression pattern, which could explain the biphasic neutrophil recruitment. Intratracheal pyrrolidine dithiocarbamate attenuated lung injury as evidenced by a reduction of neutrophil accumulation and expression of inflammatory mediators.
  
  
  CONCLUSIONS
  These data suggest that NF-kappaB binding activity plays a key role in molecular and cellular events in acid-induced lung injury.
authors.affiliation: Institute of Anesthesiology, Department of Surgery, University of Zurich, Switzerland.
authors.forename: Lilly
authors.initials: L
authors.lastname: Madjdpour
authors.forename: Sita
authors.initials: S
authors.lastname: Kneller
authors.forename: Christa
authors.initials: C
authors.lastname: Booy
authors.forename: Thomas
authors.initials: T
authors.lastname: Pasch
authors.forename: Ralph C
authors.initials: RC
authors.lastname: Schimmer
authors.forename: Beatrice
authors.initials: B
authors.lastname: Beck-Schimmer
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008168:Lung / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D011015:Pneumonia, Aspiration / Q000150:complications*; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology*; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C020972:pyrrolidine dithiocarbamic acid