title: Impact of aging on pulmonary responses to acute ozone exposure in mice: role of TNFR1.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA. sshore@hsph.harvard.edu
authors: Stephanie A
authors: SA
authors: Shore
authors: Erin S
authors: ES
authors: Williams
authors: Lucas
authors: L
authors: Chen
authors: Leandro A P
authors: LA
authors: Benedito
authors: David I
authors: DI
authors: Kasahara
authors: Ming
authors: M
authors: Zhu
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D066258:Amphiregulin; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D062506:Claudin-4; D057167:Claudins / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D066255:EGF Family of Proteins; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; C587849:Areg protein, mouse; C568157:CLDN4 protein, human; D062506:Claudin-4; D057167:Claudins; C568158:Cldn4 protein, mouse; D016207:Cytokines; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C491054:Mt2 protein, mouse; D010083:Oxidants, Photochemical; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; C525355:metallothionein-1, mouse; D010126:Ozone; D008668:Metallothionein; D051547:Heme Oxygenase-1