Antioxidant and inflammatory response after acute nitrogen dioxide and ozone exposures in C57Bl/6 mice.
Ozone (O(3)) and nitrogen dioxide (NO(2)) are highly reactive and toxic oxidant pollutants. The objective of this study is to compare chemokine, cytokine, and antioxidant changes elicited by acute exposures of O(3) and NO(2) in a genetically sensitive mouse. Eight-week-old C57Bl/6J mice were exposed to 1 or 2.5 ppm ozone or 15 or 30 ppm NO(2) for 4 or 24 h. Changes in mRNA abundance in lung were assayed by slot blot and ribonuclease protection assay (RPA). Messages encoding metallothionein (Mt), heme oxygenase I (HO-I), and inducible nitric oxide synthase (iNOS) demonstrated increased message abundance after 4 and 24 h of exposure to either O(3) or NO(2). Furthermore, increases in message abundance were of a similar magnitude for O(3) and NO(2). Messages encoding eotaxin, macrophage inflammatory protein (MIP)-1alpha, and MIP-2 were elevated after 4 and 24 h of exposure to 1 ppm ozone. Interleukin-6 was elevated after 4 h of exposure to ozone. After 4 h of 2.5 ppm ozone exposure, increased mRNAs of eotaxin, MIP-1alpha, MIP-2, Mt, HO-I, and iNOS were elevated to a higher magnitude than were detected after 1 ppm ozone. Monocyte chemoattractant protein (MCP-1) was elevated following 15 ppm NO(2) exposure. After 4 h of 30 ppm NO(2) exposure, messages encoding eotaxin, MIP-1alpha, MIP-2, and MCP-1 were elevated to levels similar to those detected after ozone exposure. Our results demonstrate a similar antioxidant and chemokine response during both O(3) and NO(2) exposure. Induction of these messages is associated with the duration and concentration of exposure. These studies suggest that these gases exert toxic action through a similar mechanism.
Johnston
C J
CJ
Department of Pediatrics, University of Rochester, 601 Elmwood Avenue, Box 777, Rochester, NY 14642, USA.
Reed
C K
CK
Avissar
N E
NE
Gelein
R
R
Finkelstein
J N
JN
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000235:genetics / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000633:toxicity*; D023282:Nuclease Protection Assays; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000633:toxicity*; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D000393:Air Pollutants; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D010083:Oxidants, Photochemical; D012333:RNA, Messenger; D010126:Ozone; D008668:Metallothionein; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D006419:Heme Oxygenase (Decyclizing); D009585:Nitrogen Dioxide