Figure 3.

The downregulation of GR expression by RU-486 counteracts the effect of Dex in protecting mice against immune-hepatic injuries. As described in Figure 2, IMH was induced in four groups of age-matched C57BL/6 mice with the indicated treatments. Then, 72 h after LPS challenge, GR expression of CD11b⁺Gr1⁺MDSC in liver was analysed by FACS (a) and the level of ALT (b) TNFα and IL-1β (c) in serum were determined by ELISA. The immunosuppressive activity of myeloid-derived CD11b⁺Gr1⁺ cells was determined by mixed lymphocyte reaction (d) Three groups of donor C57BL/6 mice were challenged with LPS, LPS plus Dex or LPS plus Dex and RU-486 (10 mg/kg, i.p.). After 3 days, a total of 1 × 10⁶ CD11b⁺Gr1⁺ cells were sorted from the liver of indicated mice and adoptively transferred into C57BL/6 recipient mice (10 mice per group) via i.v. injection. After 10–12 h, all groups of recipient mice were challenged with LPS (10 mg/kg), and mouse survival was followed (e) Data are representative of three (a–c) or two (d) independent experiments (a–d; n=3–5). ***P<0.001 compared with the indicated groups. GR, glucocorticoid receptor; IMH, immunological hepatic injury; i.p., intraperitoneal; MDSC, myeloid-derived suppressor cell; LPS, lipopolysaccharide.