RT Journal Article
SR Electronic
T1 ISOFORM-SPECIFIC EXPRESSION AND INDUCTION OF UDP-GLUCURONOSYLTRANSFERASE IN IMMUNOACTIVATED PERITONEAL MACROPHAGES OF THE RAT
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1391
OP 1398
DO 10.1124/dmd.105.004879
VO 33
IS 9
A1 Yuki Tochigi
A1 Naoko Yamashiki
A1 Satoru Ohgiya
A1 Sawako Ganaha
A1 Hiroshi Yokota
YR 2005
UL http://dmd.aspetjournals.org/content/33/9/1391.abstract
AB Phase I drug-metabolizing enzymes such as cytochrome P450 in immunocytes are known to play a role in metabolic activation of toxic and immunosuppressive compounds such as polycyclic aromatic hydrocarbon (PAH). UDP-glucuronosyltransferase (UGT), a drug-metabolizing phase II enzyme, accelerates elimination of these compounds; however, there is little information on the expression and function of UGT in immunocytes. In this study, we investigated the expressions of UGT isoforms in rat peritoneal macrophages and the role of UGT in macrophage functions. Expressions of UGT1A1, 1A6, and 1A7 were observed in macrophages by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. When macrophage cells cultured in plates were exposed to 1-naphthol and 3-hydroxybenzo-[a]pyrene (3-OH-B[a]P), these glucuronides increased in the medium, indicating that macrophages glucuronidated the chemicals. The production of the glucuronides of 1-naphthol and 3-OH-B[a]P was induced by lipopolysaccharide (LPS) treatment of the cultured macrophage cells. Northern blot analysis revealed that UGT1A7 mRNA was induced by LPS treatment. This result is the first evidence that a drug-metabolizing enzyme is induced by immunoactivation. The results indicated that macrophages can detoxify various toxic and immunosuppressive compounds with UGT, and that ability is enhanced by immunoactivation. We propose that macrophages contribute to protection against not only macromolecules as immunocytes but also small molecules such as the immunosuppressive agents PAHs in peripheral blood and interstitial tissues. The American Society for Pharmacology and Experimental Therapeutics