Abstract
Context: Chamber studies in adult humans indicate reduced responses to acute ozone with increasing age. Age-related changes in TNFα have been observed. TNFα induced inflammation is predominantly mediated through TNFR1.Objective: To examine the impact of aging on inflammatory responses to acute ozone exposure in mice and determine the role of TNFR1 in age-related differences.Materials and methods: Wildtype and TNFR1 deficient (TNFR1−/–) mice aged 7 or 39 weeks were exposed to ozone (2 ppm for 3 h). Four hours after exposure, bronchoalveolar lavage (BAL) was performed and BAL cells, cytokines, chemokines, and protein were examined.Results: Ozone-induced increases in BAL neutrophils and in neutrophil chemotactic factors were lower in 39- versus 7-week-old wildtype, but not (TNFR1−/–) mice. There was no effect of TNFR1 genotype in 7-week-old mice, but in 39-week-old mice, BAL neutrophils and BAL concentrations of MCP-1, KC, MIP-2, IL-6 and IP-10 were significantly greater following ozone exposure in TNFR1−/– versus wildtype mice. BAL concentrations of the soluble form of the TNFR1 receptor (sTNFR1) were substantially increased in 39-week-old versus 7-week-old mice, regardless of exposure.Discussion and conclusion: The data suggest that increased levels of sTNFR1 in the lungs of the 39-week-old mice may neutralize TNFα and protect these older mice against ozone-induced inflammation.
Accepted Version (
Free)
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call