title: Induction of cyclooxygenase-2 in alveolar macrophages after acid aspiration: selective cyclooxygenase-2 blockade reduces interleukin-6 production.
abstract: BACKGROUND
  Gastric acid aspiration can result in acute lung injury. In this study, the authors determined whether alveolar macrophages express cyclooxygenase-2 as a source of inflammatory mediators after acid aspiration.
  
  
  METHODS
  Seventy-five microliters of hydrochloric acid solution, pH 1.15, was instilled into one lung in mice. After exposure, alveolar macrophages were harvested, and competitive polymerase chain reaction and enzyme-linked immunosorbent assay were performed to measure expression of cyclooxygenase-1 and -2, interleukin-1beta and -6, tumor necrosis factor-alpha, and inducible nitric oxide synthase (iNOS). The authors used immunocytochemistry to demonstrate expression of cyclooxygenase-2 in alveolar macrophages. Selective cyclooxygenase-2 blockade using N-2(-cyclohexyloxy-4-nitrophenyl) methane-sulphonamide was done to characterize prostaglandin-cytokine interaction.
  
  
  RESULTS
  Acid aspiration induced upregulation of cyclooxygenase-2 and interleukin-6. Tumor necrosis factor-alpha and iNOS were not upregulated. Interleukin-1beta was upregulated even with saline instillation but could not be detected in the supernatant of the cell culture. Alveolar macrophages harvested from mice instilled with acid showed a trend toward more production of prostaglandin E2 and produced higher concentrations of interleukin-6 compared with alveolar macrophages from mice instilled with saline. Selective cyclooxygenase-2 blockade significantly decreased release of interleukin-6 from alveolar macrophages harvested from mice instilled with acid.
  
  
  CONCLUSIONS
  Acid aspiration induces strong expression of cyclooxygenase-2 and production of interleukin-6 in alveolar macrophages. Selective cyclooxygenase-2 blockade reduced production of interleukin-6 by acid-stimulated alveolar macrophages. These studies suggest that the induction of cyclooxygenase-2 plays an important role in the systemic inflammatory response induced by acid aspiration.
authors.affiliation: Department of Anesthesia, University of California, San Francisco, 94143-0542, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ohara
authors.forename: T
authors.initials: T
authors.lastname: Sawa
authors.forename: K
authors.initials: K
authors.lastname: Kurahashi
authors.forename: J P
authors.initials: JP
authors.lastname: Wiener-Kronish
authors.forename: V
authors.initials: V
authors.lastname: Doshi
authors.forename: I
authors.initials: I
authors.lastname: Kudoh
authors.forename: M A
authors.initials: MA
authors.lastname: Gropper
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic; D006851:Hydrochloric Acid / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009578:Nitrobenzenes / Q000494:pharmacology*; D010544:Peroxidases / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010544:Peroxidases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D006851:Hydrochloric Acid