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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570244 | PMC |
| http://dx.doi.org/10.1016/j.jaci.2007.03.051 | DOI Listing |
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