The IL-1 type 1 receptor is required for the development of LPS-induced airways disease.


Journal Article

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. CONCLUSION:These data support the hypothesis that signaling through the IL-1 receptor modulates extracellular matrix homeostasis in response to inhaled LPS. CLINICAL IMPLICATIONS:Attenuating IL-1R1-mediated signaling might be an effective therapy against the development of airway remodeling in chronic inflammatory diseases.

Full Text

Cited Authors

  • Brass, DM; Hollingsworth, JW; Fessler, MB; Savov, JD; Maxwell, AB; Whitehead, GS; Burch, LH; Schwartz, DA

Published Date

  • July 2007

Published In

Volume / Issue

  • 120 / 1

Start / End Page

  • 121 - 127

PubMed ID

  • 17512577

Pubmed Central ID

  • 17512577

Electronic International Standard Serial Number (EISSN)

  • 1097-6825

International Standard Serial Number (ISSN)

  • 0091-6749

Digital Object Identifier (DOI)

  • 10.1016/j.jaci.2007.03.051


  • eng