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Fig. 1 DHE directly bound to TREM2 to inhibit LPS-induced NO production in BV-2 microglial cells. (A, A′) Chemical structure of DHE and 20-Epiervatamine. (B, B′) The production of NO in the cell culture supernatant was determined by the Griess reagent assay; n = 4. (C, C′) Molecular docking of DHE (C) or 20-Epiervatamine (C′) to TREM2. (D) CETSA was carried out as described above. Cell lysates were analyzed by Western blotting. Representative images are shown. (E) The average Tm value of 6, 12, and 25 μM of DHE and 12 μM of 20-Epiervatamine. (F–I) The CETSA curves of TREM2 in BV2 cells were determined in the absence and presence of DHE (6, 12, and 25 μM) or 20-Epiervatamine (12 μM). Each band intensity of TREM2 was normalized with respect to that obtained at 37 °C. n = 3–4. Data are presented as mean ± SD analyzed by one-way ANOVA. ∗∗∗p < 0.001 vs. the LPS-treated group; ###p < 0.001 vs. the control group.