Ozone (O-3) 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 O-3 and NO...
详细信息
Ozone (O-3) 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 O-3 and NO2 in a genetically sensitive mouse. Eight-week-old C57BI/6J mice were exposed to 1 or 2.5 ppm ozone or 15 of 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 1 (HO-1), and inducible nitric oxide synthase (iNOS) demonstrated increased message abundance after 4 and 24 h of exposure to either O-3 or NO2. Furthermore, increases in message abundance were of a similar magnitude for O-3 and NO2. Messages encoding eotaxin, macrophage inflammatory protein (MIP)-1 alpha, and MIP-2 were elevated after 4 and 24 h of exposure to I 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 alpha: MIP-2, Mt, MO-1, and iNOS were elevated to a higher magnitude than were detected after I 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 alpha MIP-2, and MCP-I 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 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.
Hepatic ischemia/reperfusion injury is caused primarily by the products of neutrophils recruited into the liver after reperfusion. The mediators responsible for the development of this inflammatory response are though...
详细信息
Hepatic ischemia/reperfusion injury is caused primarily by the products of neutrophils recruited into the liver after reperfusion. The mediators responsible for the development of this inflammatory response are thought to be tumor necrosis factor-alpha and interleukin (IL)-1. Although there is abundant evidence to support a role for tumor necrosis factor-alpha, much less is known about the function of IL-1 in this injury. In the present studies, we investigated whether IL-1 was a critical mediator for the induction of liver inflammation after ischemia/reperfusion. Wild-type and IL-1 receptor I-knockout (IL-1RI(-/-)) mice were exposed to 90 minutes of partial hepatic ischemia and up to 24 hours of reperfusion. In wild-type mice, IL-1beta expression was maximal after ischemia and 8 hours of reperfusion. At the same time, both wild-type and IL-1RI(-/-) mice had severe liver injury as assessed by serum alanine aminotransferase levels and hepatic histopathology. However, IL-1RI(-/-) mice had significantly less neutrophil accumulation in liver tissues as measured by liver myeloperoxidase content and histology. The reduction in hepatic neutrophil recruitment in IL-IRI-/- mice was associated with decreased activation of the transcription factor, nuclear factor-kappaB, and reduced expression of the CXC chemokine, macrophage inflammatory protein-2. These data suggest that IL-1 functions to augment neutrophil accumulation, but does not play an essential role in this response.
暂无评论