Proinflammatory signaling inhibits FXR-dependent gene expression in mouse ileum. (A) Induction of gene expression in ileal organoids derived from CF mice (Cftr-/-) and controls (Cftr N/N). Data shown are means ± SE of 3 technical replicates per group. a, Two-way analysis of variance indicated that treatment with the FXR agonist GW4064 significantly enhanced Fgf15 expression (P = .0002), independent of genotype. (B) Induction of Fgf15 and Shp expression by GW4064 in the presence or absence of LPS, or the cytokines (CKs) interferon γ, interleukin 1β, and tumor necrosis factor α (CKs), in ileal organoids. Data show the level of gene expression relative to the level of expression in the absence of GW4064. Data shown are means ± SE of 4–6 technical replicates. b, One-way analysis of variance indicates that the combination of cytokines significantly reduced GW4064-dependent Shp expression (P = .02, Tukey multiple comparisons test). (C) Induction of Fgf15 expression by GW4064 in the presence or absence of LPS in ileal tissue. Data show the level of gene expression relative to the level of expression in the absence of GW4064. Data shown are means ± SE of 4 biological replicates. c, One-way analysis of variance indicates that LPS significantly reduced GW4064-dependent Fgf15 expression (P = .007, Tukey multiple comparisons test).