Figure 7. STING increases HSC activation status and enables macrophage factors to enhance HSC activation (A, B, C).

Activating STING enhances HSC activation. For A - C, LX2 cells were treated with or without DMXAA (75 µg/mL) in the absence or presence of TGFβ1 (8 ng/mL) for 24 hr (A and C (top panel)) or TGFβ1 (2.5 ng/mL) for 48 hr (B and C (bottom panel)). (D, E) STING-driven macrophage factors enhance HSC activation. For D, LX2 cells were co-cultured with STING^gt BMDM and/or WT BMDM that were pre-treated with DMXAA (75 µg/mL) or Ctrl for 24 hr. The co-cultures were incubated for 48 hr in the absence or presence of TGFβ1 (2.5 ng/mL). For E, LX2 cells were treated with conditioned media (CM) of DMXAA (DMX)- or Ctrl-treated WT BMDM and/or STING^gt BMDM for 48 hr. For A, B, and D, cell lysates were subjected to Western blot analysis. Bar graphs, quantification of blots. For C and E, the expression of fibrogenic genes was examined using real-time RT-PCR. For bar graphs in A - E, data are means SD. n = 4 – 6 (A, B, and D) or 6 – 8 (C and E). *, P < 0.05 and **, P < 0.01 DMXAA vs. Control (Ctrl) under the same condition (in A and B) or for the same gene (in C), co-cultures with DMX/WT BMDM vs. co-cultures with Ctrl/WT BMDM under the same condition (in D), or DMX/WT BMDM-CM-treated HSCs vs. Ctrl/WT BMDM-CM-treated HSCs for the same gene (in E); ^†, P < 0.05 and ^††, P < 0.01 TGFβ1 vs. Ctrl with the same treatment (in A, B, and D); ^‡, P < 0.05 DMX/STING^gt BMDM-CM-treated HSCs vs. DMX/WT BMDM-CM-treated HSCs under TGFβ1-stimulated condition (in D) or for the same gene (in E).