Expression of UDP-glucuronosyltransferase isoform mRNAs during inflammation and infection in mouse liver and kidney.
Inflammation or infection down-regulates the activity and expression of cytochrome P450 (P450) enzymes involved in hepatic drug clearance, possibly altering drug effectiveness and leading to toxicity. The regulation of UDP-glucuronosyltransferases (UGTs) in inflammation and infection is less well characterized. To determine the response of hepatic and renal UGTs during inflammation and infection, mice were administered either saline or 1 mg/kg lipopolysaccharide (LPS) (16 h), or Citrobacter rodentium by oral gavage (6 days). Hepatic mRNA expression of UGT1A1, 1A9, and 2B5 was similarly down-regulated after LPS exposure and C. rodentium infection, whereas UGT1A2 and 1A6 mRNAs were unchanged. Effects of C. rodentium infection did not require a functional Toll-like receptor 4. Conversely, renal UGT isoforms were relatively unaffected, except for UGT2B5 induction after LPS treatment. Regulation of UGTs during the inflammatory response exhibits similarities to and differences from regulation of P450s, and may be cytokine-mediated.
Richardson
Terrilyn A
TA
Department of Pharmacology, Emory University School of Medicine, 5119 Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322, USA.
Sherman
Melanie
M
Kalman
Daniel
D
Morgan
Edward T
ET
D000818:Animals; D015153:Blotting, Western; D044082:Citrobacter rodentium / Q000254:growth & development; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000201:enzymology* / Q000382:microbiology; D004927:Escherichia coli Infections / Q000201:enzymology / Q000382:microbiology; D005260:Female; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D006505:Hepatitis / Q000201:enzymology* / Q000382:microbiology; D007527:Isoenzymes / Q000096:biosynthesis; D007668:Kidney / Q000201:enzymology; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000201:enzymology*; D009393:Nephritis / Q000201:enzymology* / Q000382:microbiology; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014453:Glucuronosyltransferase