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Ozone enhances pulmonary innate immune response to a Toll-like receptor-2 agonist.


ABSTRACT: Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases Toll-like receptor-4 (TLR4)-mediated responses to subsequent stimulation with LPS. To explore the pulmonary innate immune response to ozone exposure further, we investigated the effects of ozone in combination with Pam3CYS, a synthetic TLR2/TLR1 agonist. Whole-lung lavage (WLL) and lung tissue were harvested from C57BL/6 mice after exposure to ozone or filtered air, followed by saline or Pam3CYS 24 hours later. Cells and cytokines in the WLL, the surface expression of TLRs on macrophages, and lung RNA genomic expression profiles were examined. We demonstrated an increased WLL cell influx, increased IL-6 and chemokine KC (Cxcl1), and decreased macrophage inflammatory protein (MIP)-1? and TNF-? in response to Pam3CYS as a result of ozone pre-exposure. We also observed the increased cell surface expression of TLR4, TLR2, and TLR1 on macrophages as a result of ozone alone or in combination with Pam3CYS. Gene expression analysis of lung tissue revealed a significant increase in the expression of genes related to injury repair and the cell cycle as a result of ozone alone or in combination with Pam3CYS. Our results extend previous findings with ozone/LPS to other TLR ligands, and suggest that the ozone priming of innate immunity is a general mechanism. Gene expression profiling of lung tissue identified transcriptional networks and genes that contribute to the priming of innate immunity at the molecular level.

SUBMITTER: Oakes JL 

PROVIDER: S-EPMC3547086 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Ozone enhances pulmonary innate immune response to a Toll-like receptor-2 agonist.

Oakes Judy L JL   O'Connor Brian P BP   Warg Laura A LA   Burton Rachel R   Hock Ashley A   Loader Joan J   Laflamme Daniel D   Jing Jian J   Hui Lucy L   Schwartz David A DA   Yang Ivana V IV  

American journal of respiratory cell and molecular biology 20120920 1


Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases Toll-like receptor-4 (TLR4)-mediated responses to subsequent stimulation with LPS. To explore the pulmonary innate immune response to ozone exposure further, we investigated the effects of ozone in combination with Pam3CYS, a synthetic TLR2/TLR1 agonist. Whole-lung lavage (WLL) and lung tissue were harvested from C57BL/6 mice after exposure to ozone or filtered air, followed by saline or Pam3CYS 24 hours l  ...[more]

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