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. Author manuscript; available in PMC: 2015 Aug 21.
Published in final edited form as: Immunity. 2014 Jul 24;41(2):296–310. doi: 10.1016/j.immuni.2014.06.014

Figure 1. Commensal derived indole metabolite, IPA, regulates PXR activation.

Figure 1

(A) Transcriptional activity of a PXR reporter gene (multi-drug resistance-associated protein 2 or MRP2 luciferase) co-transfected with mPXR (black) and hPXR (red) expression plasmids in 293T cells following treatment with IPA (n=3). RLU, relative light unit.

(B) Transcriptional activity of a PXR reporter gene (MRP2 luciferase) co-transfected with hPXR expression plasmid in 293T cells following treatment with fixed concentration of indole (1 mM) and increasing concentrations of IPA (n=3). RLU, relative light unit. Data expressed as fold change in RLU compared to vehicle (DMSO) controls.

(C) Real-time qPCR analysis of Mdr-1 expression in Nr1i2+/+ and Nr1i2−/− mice jejunum villi enterocytes following oral treatment with IPA (20 mg/kg/day) (n=5 per group). *P ≤ 0.0001; **P ≤ 0.001;n.s. not significant (Two-way ANOVA with Tukey’s multiple comparison test).

(D) Schematic of germ free mouse treatment schedule. Six treatment groups are shown by color code: Swiss Webster Germ Free mice (SWGF) group, administered 100 μl LB and 100 μl sterilized water by oral gavage; SWGF + tryptophan (Trp) group, administered 100 μl LB + L-tryptophan; SWGF + Heat-killed C. sporogenes (C.s) group, administered C.s by oral gavage; SWGF + (C.s) group, administered C.s by oral gavage; SWGF + Heat-killed (C.s) + Trp group; and SWGF + C.s + Trp group, administered C.s and Trp by oral gavage (see Experimental Procedures). All the treatments were scheduled for six sequential days.

(E) Plasma IPA peak area intensity values plotted by treatment group as illustrated in the schema (D) Color coded histograms show mean ± s.e.m. values pertaining to each treatment group. IPA concentrations in micromoles (μM) are listed by color code.

(F) erum FITC-dextran recovery in treatment groups illustrated in schema (D).

*P ≤ 0.0001; (Two-way ANOVA with Tukey’s multiple comparison test ); (n=6 per group).

(G) Real-time qPCR analysis of Mdr1, Cyp3a11 and Ugt1a1 mRNA expression in small intestinal mucosa from schema (D). All graphs show mean values ± s.e.m. Also see Figure S1,Table S1 and supplemental movies S1 and S2.