title: The IL-1 type 1 receptor is required for the development of LPS-induced airways disease.
abstract: BACKGROUND
  The contribution of IL-1beta signaling through the IL-1 type 1 receptor (IL-1R1) to the development of persistent LPS-induced airway disease has not been investigated.
  
  
  OBJECTIVE
  To determine the importance of signaling through the IL-1 type 1 receptor in the development of LPS-induced airway disease.
  
  
  METHODS
  We exposed IL-1R1-deficient (C57BL/6(IL-1RI-/-)) mice to an aerosol of LPS or filtered air for 1 day, 1 week, or 4 weeks.
  
  
  RESULTS
  After 4 weeks of LPS inhalation, C57BL/6(IL-1RI-/-) mice failed to develop significant submucosal thickening, whereas C57BL/6 mice had significantly thickened submucosa in small, medium, and large airways compared with those of unexposed control mice. Cell proliferation in the airways of both the 1-week and 4-week LPS-exposed C57BL/6(IL-1RI-/-) mice was significantly reduced compared with LPS-exposed C57BL/6 mice. mRNA for type III alpha-3 procollagen was significantly elevated over baseline in C57BL/6 yet remained unchanged compared with baseline in C57BL/6(IL-1RI-/-) mice after 1 week or 4 weeks of LPS inhalation. mRNA for tissue inhibitor of metalloprotease 1 in C57BL/6 mice in the 1-week and 4-week groups was significantly elevated over both control mice and C57BL/6(IL-1RI-/-) mice.
  
  
  CONCLUSIONS
  These data support the hypothesis that signaling through the IL-1 receptor modulates extracellular matrix homeostasis in response to inhaled LPS.
  
  
  CONCLUSIONS
  Attenuating IL-1R1-mediated signaling might be an effective therapy against the development of airway remodeling in chronic inflammatory diseases.
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. brassd@niehs.nih.gov
authors.forename: David M
authors.initials: DM
authors.lastname: Brass
authors.forename: John W
authors.initials: JW
authors.lastname: Hollingsworth
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fessler
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Savov
authors.forename: Abby B
authors.initials: AB
authors.lastname: Maxwell
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Whitehead
authors.forename: Lauranell H
authors.initials: LH
authors.lastname: Burch
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018375:Neutrophil Activation; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D016326:Extracellular Matrix Proteins; D008070:Lipopolysaccharides; D053573:Receptors, Interleukin-1 Type I; D053773:Transforming Growth Factor beta1