Figure 6.

PAH inhibits cGAS-mediated autoimmunity in mice. (A) BMDMs from Trex1 ^+/+ or Trex1^−/− mice were treated with different PAH doses (0 to 250 μM) for 6 h, then the cell lysates were immunoblotted with the indicated antibodies. (B) BMDMs from Trex1^−/− mice were treated with indicated concentrations of PAH. The baseline of Ifnb, Cxcl10, Isg15, Isg56, Ifit2, Ifit3, and Ifi44 mRNA expression was then measured by qPCR. (C) Schematic of Trex1^−/− mice drug administration in vivo. 4 weeks old Trex1^−/− mice were orally administered Vehicle (0.03% CMC-Na solution) or 120 mg• kg⁻¹ PAH once per day for 14 days. (D–G) The levels of Cxcl10, Isg15, Isg56, and Ifit3 mRNA expression in the heart (D), spleen (E), stomach (F), and tongue (G) of mice treated in (C) were measured by qPCR. (H) Representative autoantibodies blotting band of heart extracts from WT mice. Heart extracts were blotted with serum from Trex1 ^+/+, Trex1^{− / −} (Vehicle), and Trex1^{− / −} (PAH) mice and detected using HRP-conjugated anti-mouse IgG. (I) Representative H&E-stained heart tissue sections from Trex1 ^+/+, Trex1^–/– (Vehicle), and Trex1^–/– (PAH) mice. Scale bars represent 100 μm. (J) Pathological scores of cardiac inflammations in Trex1^{− / −} mice administrated with the Vehicle or PAH for 14 days. Data in (A, B) were repeated at least three times, data in (D–J) are representative of two independent experiments. Data in (B, D–G) are presented as mean ± SD. *P< 0.05, **P< 0.01, ***P < 0.001.