RESUMO
The role of high mobility group box 1 (HMGB1) in the regulation of efflux transporters in the liver and kidney remains unclear, although it has been reported that HMGB1 can increase Pglycoprotein (Pgp) expression in the brain. The present study aimed to clarify the involvement of HMGB1 in the regulation of Pgp expression in the liver and kidney of mice with lipopolysaccharide (LPS)induced inflammation. Mice were treated with LPS or LPS + glycyrrhizin (GL); GL is as an HMGB1 inhibitor. Subsequently, the expression levels of transporters, such as Pgp, and HMGB1 receptors, such as tolllike receptor (TLR)4 and receptor for advanced glycation endproducts (RAGE), were determined by quantitative PCR and LCMS/MSbased targeted proteomics. For the in vitro study, HepG2 and KMRC1 cells were used, as was a coculture of KMRC1 and differentiated THP1 cells. The mRNA and protein expression levels of Mdr1a and Tlr4 in the kidneys of LPS + GLtreated mice were significantly decreased compared with those in LPS mice. The results indicated that HMGB1 had little effect on the expression of Mdr1a and Tlr4 in the liver, since there was little change in of Mdr1a and Mdr1b expression between the LPS and LPS + GLtreated mice. Notably, regarding MDR1 mRNA expression, KMRC1 cells were more responsive to LPS than HepG2 cells, and KMRC1 cells treated with LPS exhibited increased levels compared with control KMRC1 cells. In differentiated THP1 cells, LPS treatment decreased the mRNA expression levels of TLR4, whereas they were restored to control levels by HMGB1. In conclusion, HMGB1 in the plasma and TLR4 in macrophages may be involved in the regulation of Pgp expression in the kidneys of inflamed mice.