Airway inflammation and responsiveness in prostaglandin H synthase-deficient mice exposed to bacterial lipopolysaccharide

Am J Respir Cell Mol Biol. 2001 Oct;25(4):457-65. doi: 10.1165/ajrcmb.25.4.4505.


Bacterial lipopolysaccharide (LPS) is a risk factor for exacerbation of asthma and causes airway inflammation. The aim of this study was to examine the effects of disruption of prostaglandin (PG) H synthase (PGHS)-1 and PGHS-2 genes on pulmonary responses to inhaled LPS. PGHS-1(-/-), PGHS-2(-/-), and wild-type (WT) mice were exposed to 4 to 6 microg/m(3) LPS via aerosol. Enhanced pause (PenH), a measure of bronchoconstriction, was assessed using a whole-body plethysmograph before and immediately after a 4-h LPS exposure. Bronchoalveolar lavage (BAL) was performed after LPS exposure to assess inflammatory cells, cytokines/chemokines (tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2), and PGE(2). The degree of lung inflammation was scored on hematoxylin-and-eosin-stained sections. PGHS-1 and PGHS-2 protein levels were determined by immunoblotting. All mice exhibited increased PenH and methacholine responsiveness after LPS exposure; however, these changes were much more pronounced in PGHS-1(-/-) and PGHS-2(-/-) mice relative to WT mice (P < 0.05). There were no significant differences in inflammation as assessed by BAL fluid (BALF) cells or lung histology between the genotypes despite reduced BALF cytokines/chemokines and PGE(2) in PGHS-1(-/-) and PGHS-2(-/-) mice relative to WT mice (P < 0.05). PGHS-2 was upregulated more in PGHS-1(-/-) mice compared with WT mice after LPS exposure. We conclude that: (1) airway inflammation and hyperresponsiveness are dissociated in PGHS-1(-/-) and PGHS-2(-/-) mice exposed to LPS; (2) the balance of PGHS-1 and PGHS-2 is important in regulating the functional respiratory responses to inhaled LPS; and (3) neither PGHS-1 nor PGHS-2 is important in regulating basal lung function or the inflammatory responses of the lung to inhaled LPS.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Chemokines / metabolism
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cytokines / metabolism
  • Dinoprostone / biosynthesis
  • Disease Models, Animal
  • Female
  • Isoenzymes / drug effects
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Leukotriene B4 / biosynthesis
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology*
  • Lung / pathology
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Pneumonia / chemically induced
  • Pneumonia / physiopathology*
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Proteins / metabolism
  • Up-Regulation


  • Chemokines
  • Cytokines
  • Isoenzymes
  • Lipopolysaccharides
  • Membrane Proteins
  • Proteins
  • Leukotriene B4
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • Dinoprostone