ANTIOXIDANT AND INFLAMMATORY RESPONSE AFTER ACUTE NITROGEN DIOXIDE AND OZONE EXPOSURES IN C57Bl/6 MICE

Abstract

Ozone (O₃) and nitrogen dioxide (NO₂) 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 O₃ and NO₂ in a genetically sensitive mouse. Eight-weekold C57Bl/6J mice were exposed to 1 or 2.5 ppm ozone or 15 or 30 ppm NO₂ 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 O₃ or NO₂. Furthermore, increases in message abundance were of a similar magnitude for O₃ and NO₂. Messages encoding eotaxin, macrophage inflammatory protein (MIP)-1 a, 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-1 a, 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 NO₂ exposure. After 4 h of 30 ppm NO₂ exposure, messages encoding eotaxin, MIP-1 a, 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 O₃ and NO₂ 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.