Differential proinflammatory cytokine responses of the lung to ozone and lipopolysaccharide exposure during postnatal development.
Age appears to be a critical variable in the ability of the lung to cope with external stress. Alterations in cellular responses associated with environmental toxicants are likely to modify the developmental processes. This would suggest that the timing and interaction between exposure and developmental events appears to play an important role as susceptible targets for environmental perturbation. C57BL/6 mice ages 2, 4, 7, 10, 14, 28, and 56 days were exposed to 2.5 PPM ozone for 4 hours or to a 10-minute inhalation of lipopolysaccharide (LPS) with an estimated deposited dose of 26 EU and examined 2 hours post exposure. Abundance of proinflammatory cytokine and chemokine mRNA were measured by RNase protection assay. After ozone exposure interleukin (IL)-6 was not detected in 2-, 4-, and 7-day-old mice; however, increases of 18- to 20-fold were measured in 10-, 14-, 28-, and 56-day-old mice. Macrophage inhibitory protein (MIP)-2 and cytokine-induced neutrophil chenocettractant (KC) were elevated slightly, with no differences between 2- and 56-day-old mice. After LPS exposure, IL-6 was not detected in 2- and 4-day-old mice; however, 8- to 10-fold increases were measured in 7-, 14-, and 28-day-old mice and approximately 20-fold in 56-day-old mice. IL-1beta was elevated approximately 4-fold at 2 and 4 days of age but was elevated 25- to 30-fold in 7-, 14-, 28-, and 56-day-old mice. MIP-2 and KC mRNA abundance was elevated 25- to 30-fold, with no differences between 2- and 56-day-old mice. These results demonstrate that critical time points exist during lung development to inhaled environmental pollutants and that differences exist in the maturation of inflammatory and epithelial defense mechanisms.
Johnston
Carl J
CJ
Department of Environmental Medicine, University of Rochester, NY 14642, USACarl_Johnston@urmc.rochester.edu
Holm
Bruce A
BA
Finkelstein
Jacob N
JN
D000818:Animals; D015415:Biomarkers; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics*; D003423:Critical Period, Psychological; D015870:Gene Expression / Q000276:immunology; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000254:growth & development / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010126:Ozone / Q000494:pharmacology*; D011014:Pneumonia / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D013047:Specific Pathogen-Free Organisms
D015415:Biomarkers; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D010126:Ozone