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Increases in the serum acute phase proteins after ozone exposure are associated with induction of genes in the lung but not liver
Citation:
Henriquez, A., D. Miller, M. Schladweiler, J. Richards, AND U. Kodavanti. Increases in the serum acute phase proteins after ozone exposure are associated with induction of genes in the lung but not liver. Presented at Society of Toxicology, Phoenix, AZ, March 23 - 27, 2014.
Impact/Purpose:
Systemic response to air pollution is linked to metabolic syndrome. This study shows that major acute phase response genes are induced in the lung but not liver after ozone exposure suggesting that the role of lung could be substantial in producing systemic acute phase response after inhalation of pollutants.
Description:
Acute Phase Response (APR), a systemic reaction to infection, trauma, and inflammation, is characterized by increases and decreases in plasma levels of positive and negative acute phase proteins (APP), respectively. Although the liver has been shown to contribute to APR in various pathologies, the source of circulating APP after air pollution exposure is not well characterized. We hypothesized that lungs and liver both will contribute to plasma levels APP after an acute ozone exposure. To test this hypothesis, we exposed male Wistar Kyoto rats to air or O3 (1ppm), 6hr/day for 1 or 2 consecutive days. Immediately after ozone exposure, genes encoding APP were analyzed at mRNA level in the lungs and livers and proteins were analyzed in the serum. Ozone exposure increased positive acute phase proteins in the serum, such as α-1-acid glycoprotein, AGP; α-2-macroglobulin, A2M; and decreased negative APP such as transferrin. These increases in serum proteins were associated with marked increases in mRNA expression of several APP in the lungs (A2M, AGP, α-1-antitrypsin, hepsidin, and ceruloplasmin). Ozone did not increase liver mRNA for any APP examined. However, there were remarkable tissue differences between lung and liver mRNA expression of APP in air exposed rats (liver>lung). C-reactive protein was expressed highly in the liver but minimal expression was noted in the lung (not affected by ozone in lung or liver). Thus, although liver tissue mass is ~15 times greater than lung mass, it is clear that the acute phase protein genes are induced only in the lung after ozone exposure; the role of lung should not be ignored in modulating APR and release of APP in the circulation upon the inhalation of pollutants. (This abstract does not reflect the US EPA policy).