Figure 1.

Bile acids inhibit LPS-induced nitrite production in cell cultures. (a) Transcript expression of iNOS was determined in Raw264.7 cells, pretreated with TLCA (20 or 40 µM), TUDCA (200 µM) or BAY11-7042 (5 µM) for 2 h; LPS (50 ng/ml) was added and incubated for 24 h. Concentrations of iNOS transcripts were normalized to expression of RPS29 and the control condition without LPS (mean ± SEM, n ≥ 4 experiments). ANOVA revealed significant treatment effects on iNOS expression [F (7, 31) = 11.9, p < 0.001). (b) Nitrite production (in µM) by Raw264.7 cells was strongly induced by LPS and significantly inhibited by TLCA and the specific TGR5 agonist RG-239 (2 µM) [F (5, 20) = 15.0), p < 0.001]. (c) In microglia primary cultures, nitrite release (µM) was also induced by LPS (10 ng/ml) and inhibited by bile acids [F (7, 73) = 15.9, p < 0.001]. Statistical significance of post hoc Dunnett's tests is indicated significance between treatments and the controls ***p < 0.001 (control vs. LPS) and # p < 0.05, ##p < 0.01 and ###p < 0.001 (LPS vs. LPS + treatment).