Impact of aging on pulmonary responses to acute ozone exposure in mice: Role of TNFR1

Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Inhalation Toxicology (Impact Factor: 2.26). 11/2011; 23(14):878-88. DOI: 10.3109/08958378.2011.622316
Source: PubMed


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.
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.
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.
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.
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.

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    • "However, not all studies of young and old animals have shown a similar pattern. Several investigators [27]–[30] have examined the effects of ozone, another powerful oxidant, in mice and rats and found that older animals showed either lesser functional decrements and lesser inflammatory responses compared to younger animals or no differences. Shore et al [27] found that levels of soluble TNF receptor 1 were increased in the older animals, and suggested that that this phenomenon might account for the decreased inflammatory response. "
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