Objective        To determine the effect of plasma membrane-bound G protein-coupled receptor for bile acids (TGR5) activation by oleanolic acid (OA) on the expression of interleukin-1β （IL-1β）

tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6）in mouse macrophages.       Methods        Real-time PCR was used to detect the expression of IL-1β

TNF-α and IL-6 at mRNA level after rat macrophage RAW264.7 cells and Kuffer cells were incubated with OA in different time periods. And the expression of these inflammatory factors were further analyzed by the same method when RAW264.7 cells were stimulated by inhibitors of 3 different signal pathway plus OA. The phosphorylation level of p38 MAPK was measured by Western blotting.        Results        Treatment of RAW264.7 cells with OA resulted in a robust increase in IL-1β

IL-6 and TNF-α transcripts at 6

12 and 24 h compared with untreated control cells. Similarly

an up-regulation of IL-1β

IL-6 and TNF-α expression was also observed in isolated Kupffer cells at 3 and 6 h. Pre-treatment of RAW 264.7 cells with a p38 MAPK inhibitor SB203580 markedly reduced the OA-induced increase of IL-1β and TNF-α transcription

but not for PKA or NF-κB inhibitors. p38 phosphorylation was increased by OA treatment in both RAW 264.7 cells and Kupffer cells.        Conclusion        TGR5 activation induces IL-1β

IL-6 and TNF-α expression through p38 MAPK activation

indicating that TGR5 possesses pro-inflammatory properties when without any other stimulus.