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

Brass, DM and Spencer, JC and Li, Z and Potts-Kant, E and Reilly, SM and Dunkel, MK and Latoche, JD and Auten, RL and Hollingsworth, JW and Fattman, CL (2012) Innate immune activation by inhaled lipopolysaccharide, independent of oxidative stress, exacerbates silica-induced pulmonary fibrosis in mice. PLoS ONE, 7 (7).

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Abstract

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. © 2012 Brass et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Brass, DM
Spencer, JC
Li, Z
Potts-Kant, E
Reilly, SM
Dunkel, MK
Latoche, JDjdl10@pitt.eduJDL10
Auten, RL
Hollingsworth, JW
Fattman, CLcfattman@pitt.eduCFATTMAN
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorRyffel, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 16 July 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0040789
Schools and Programs: School of Public Health > Environmental and Occupational Health
Refereed: Yes
Other ID: NLM PMC3397936
PubMed Central ID: PMC3397936
PubMed ID: 22815821
Date Deposited: 05 Oct 2012 19:09
Last Modified: 03 Apr 2019 15:00
URI: http://d-scholarship.pitt.edu/id/eprint/15590

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