Innate immune activation by inhaled lipopolysaccharide, independent of oxidative stress, exacerbates silica-induced pulmonary fibrosis in mice.

Published

Journal Article

Acute exacerbations of pulmonary fibrosis are characterized by rapid decrements in lung function. Environmental factors that may contribute to acute exacerbations remain poorly understood. We have previously demonstrated that exposure to inhaled lipopolysaccharide (LPS) induces expression of genes associated with fibrosis. To address whether exposure to LPS could exacerbate fibrosis, we exposed male C57BL/6 mice to crystalline silica, or vehicle, followed 28 days later by LPS or saline inhalation. We observed that mice receiving both silica and LPS had significantly more total inflammatory cells, more whole lung lavage MCP-1, MIP-2, KC and IL-1β, more evidence of oxidative stress and more total lung hydroxyproline than mice receiving either LPS alone, or silica alone. Blocking oxidative stress with N-acetylcysteine attenuated whole lung inflammation but had no effect on total lung hydroxyproline. These observations suggest that exposure to innate immune stimuli, such as LPS in the environment, may exacerbate stable pulmonary fibrosis via mechanisms that are independent of inflammation and oxidative stress.

Full Text

Cited Authors

  • Brass, DM; Spencer, JC; Li, Z; Potts-Kant, E; Reilly, SM; Dunkel, MK; Latoche, JD; Auten, RL; Hollingsworth, JW; Fattman, CL

Published Date

  • January 2012

Published In

Volume / Issue

  • 7 / 7

Start / End Page

  • e40789 -

PubMed ID

  • 22815821

Pubmed Central ID

  • 22815821

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0040789

Language

  • eng