RESULTS: Mice were exposed to filtered air, 20 mg/m3
DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit
pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H.
Tumor necrosis factor is not required for particle-induced genotoxicity and
pulmonary inflammation., Arch. Toxicol. 79 (2005) 177-182). As a positive control for the induction of an
acute phase response, mice were exposed to 12.5 mg/kg of
lipopolysaccharide (LPS) intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic
mRNA expression of
acute phase proteins, serum
amyloid P (Sap) (the murine homologue of Crp) and Saa1 and Saa3. While significant increases in the hepatic expression of Sap, Saa1 and Saa3 were observed in response to LPS, their levels did not change in response to
DEP or CB. In a comprehensive search for markers of an
acute phase response, we analyzed liver tissue from these mice using high density
DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to
DEP or CB. The
mRNA expression of three of the genes (
serine (or
cysteine) proteinase inhibitor, clade A, member 3C,
apolipoprotein E and transmembrane emp24 domain containing 3) responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT-PCR.
CONCLUSION: Our findings collectively suggest that Sap, Saa1 and Saa3 are not induced in livers of mice exposed to
DEP or CB. Despite
pulmonary inflammation in these mice, global transcriptional profiling of liver did not reveal any hepatic response following exposure by inhalation.