Fig 2: The expression and activity of IDO1 and TDO in atherosclerotic blood samples. Serum concentrations of tryptophan (a) and kynurenine (b) and the kynurenine to tryptophan ratio Kyn/Trp (c) in blood samples of atherosclerotic patients with different histological classification grades ((-): n = 10, I: n = 16, II: n = 18, III: n = 7). d, e IDO1 and TDO protein levels were determined by western blot assays. f Associations between the expression of IDO1 and TDO and the concentration of Trp (r = -0.44028, *p < 0.05; r = -0.45339, *p < 0.05). g IDO1 and TDO mRNA expression was determined by real-time PCR ((-): n = 6, I/II: n = 12, III: n = 4). Data were based on at least three independent experiments. *p < 0.05

Fig 3: Before and after oxLDL treatment, the IFN-?-mediated promotion of THP-M foaming was reversed by IDO1 inhibition. a, b IDO1 activity (Kyn/Trp) was detected by HPLC. c, d The results of Oil red O staining (×400). The designation of different treatments, such as oxLDL, IFN-?, IFN-?+oxLDL, oxLDL+IFN-?, IFN-?+Incyte+oxLDL, oxLDL+IFN-?+Incyte, IFN-?+1-MT+oxLDL and oxLDL+IFN-?+1-MT, was described in the Materials and Methods. Data were based on at least three independent experiments. *p < 0.05

Fig 4: IDO1 and TDO were expressed in atherosclerotic lesions and codistributed with CD3-positive lymphocytes and CD68-positive macrophages in patients with advanced atherosclerosis. a Pathological changes of the coronary artery were revealed by HE staining (×400). b, c IDO1, TDO and the lymphocyte marker CD3 were detected in atherosclerotic lesions by immunostaining analysis (×400). d, e IDO1, TDO and the monocyte marker CD68 were detected in atherosclerotic lesions by immunostaining analysis (×400). The top panel in b–e exhibits an enlarged view of the representative region in the bottom panel

Fig 5: Inhibition of serine protease activity. (A–C) The charts illustrate the expression relative to baseline (logarithmic scale) of (A) IDO1, (B) IL1B, (C) IL6 and the effects of vehicle (open bars), 10 ng/mL LPS (black bars) or 20 nM subtilisin (red/shaded bars). The inhibitors tested were TPCK (100 µM), TLCK (100 µM) and carfilzomib 20 nM (Carf). (D–F) The charts show a comparison of the effects of TPCK (30 µM) on the induction of IDO1 (D), IL1B (E) and IL6 (F) by LPS (10 ng/mL), subtilisin (20 nM), PSA (100 nM), CD26/DPP4 (10 nM) and HtrA (10 nM). Expression is shown for vehicle (open bars) and TPCK (30 µM) (red/shaded bars) treatments. Charts show the mean ± s.e.m. (n ? 3 donors). *P < 0.05, **P < 0.01; ***P < 0.001.