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. Author manuscript; available in PMC: 2021 Jan 27.
Published in final edited form as: Nat Microbiol. 2020 Jul 27;5(11):1319–1329. doi: 10.1038/s41564-020-0763-4

Fig. 3. Immunomodulatory activities of the colipterins.

Fig. 3.

a, BioMap® phenotypic profiling assays of colipterins (single dose) against human primary cells. Cell types and stimuli used in each system are as follows: 3C system [HUVEC +(IL-1β, TNF-α and IFN-γ)], 4H system [HUVEC +(IL-4 and histamine)], LPS system [PBMC and HUVEC + LPS (TLR4 ligand)], SAg system [PBMC and HUVEC + TCR ligands (1×)], BT system [CD19+ B cells and PBMC + (α-IgM and TCR ligands (0.001×))], BF4T system [bronchial epithelial cells and HDFn + (TNF-α and IL-4)], BE3C system [bronchial epithelial cells + (IL-1β, TNF-α and IFN-γ)], CASM3C system [coronary artery smooth muscle cells + (IL-1β, TNF-α and IFN-γ)], HDF3CGF system [HDFn + (IL-1β, TNF-α, IFN-γ, EGF, bFGF and PDGF-BB)], KF3CT system [keratinocytes and HDFn + (IL-1β, TNF-α and IFN-γ)], MyoF system [differentiated lung myofibroblasts + (TNF-α and TGF-β)] and /Mphg system [HUVEC and M1 macrophages + Zymosan (TLR2 ligand)]. b, Dose response (17, 1, 0.1, 0.01, and 0.001 μM) analysis of IL-8 levels (pg ml−1) in macrophage-like cells differentiated from human THP-1 cells in the presence of 1–6. c, Dose response (17, 1, 0.1, 0.01, and 0.001 μM) analysis of IL-10 levels (pg ml−1) in mouse BMDM cells by 1-6. L-Ascorbic acid was used as a positive control. Error bars for b and c are represented as the mean ± s.e.m., n = 3. P values between DMSO and other treatments were determined by unpaired, one-way ANOVA with Dunnett’s test. d, Stable DPPH radical scavenging activities of 1-6. 3a and 4a are chemically reduced tetrahydropterin-variants of 3 and 4, respectively. Tetrahydropteron (THP) and L-ascorbic acid were used as positive controls. Data are presented by mean ± s.d. (n = 3). e, Disk diffusion test of 3, 4, 6, pterin, and THP against E. coli Nissle1917 in the presence of hydrogen peroxide. 100 μg/disk of compound was treated, incubated for 3 h at 37 °C, and 1 μl of 30% H2O2 was subsequently added on the disk. P value was determined by a two-tailed unpaired t-test. The mean and s.d. are presented from three biological replicates (n = 3).