Figure 5
Figure 5. Inhibition of PKCα and θ reduces alloreactive chemokine receptor expression and inflammatory cytokine production in vivo. Total-body irradiation (800 cGy) was dosed to BALB/c mice, which were then transplanted with 5 × 106 WT C57BL/6 TCD-BM cells alone (n = 2 per experiment) or in addition to 1 × 106 total T cells and treated twice daily by gavage with vehicle or 40 mg/kg R524 (n = 4 per group per experiment) beginning on day 0 and continuing daily for 2 weeks. Fourteen days posttransplant, recipient spleens, livers, and lungs were harvested; organ cell counts determined; and samples stained for H2Kb, CD4, CD8, CXCR3, CCR6, IFN-γ, and TNF-α. Average percentages ± SEM are based on live H2Kb+ (donor) cell gate (A), T-cell chemokine receptor expression (B), and intracellular T-cell cytokine expression (C). Serum collected at necropsy was subjected to cytokine bead analysis (D) to quantify serum cytokine concentrations of IFN, TNF, IL-2, IL-6, IL-10, and IL-17. Cytokines that are not graphically represented were undetectable in serum. Data are representative of 1 experiment out of 3 separate repeat experiments. *P < .05; **P < .01; ***P < .001 (compared with vehicle-treated controls).

Inhibition of PKCα and θ reduces alloreactive chemokine receptor expression and inflammatory cytokine production in vivo. Total-body irradiation (800 cGy) was dosed to BALB/c mice, which were then transplanted with 5 × 106 WT C57BL/6 TCD-BM cells alone (n = 2 per experiment) or in addition to 1 × 106 total T cells and treated twice daily by gavage with vehicle or 40 mg/kg R524 (n = 4 per group per experiment) beginning on day 0 and continuing daily for 2 weeks. Fourteen days posttransplant, recipient spleens, livers, and lungs were harvested; organ cell counts determined; and samples stained for H2Kb, CD4, CD8, CXCR3, CCR6, IFN-γ, and TNF-α. Average percentages ± SEM are based on live H2Kb+ (donor) cell gate (A), T-cell chemokine receptor expression (B), and intracellular T-cell cytokine expression (C). Serum collected at necropsy was subjected to cytokine bead analysis (D) to quantify serum cytokine concentrations of IFN, TNF, IL-2, IL-6, IL-10, and IL-17. Cytokines that are not graphically represented were undetectable in serum. Data are representative of 1 experiment out of 3 separate repeat experiments. *P < .05; **P < .01; ***P < .001 (compared with vehicle-treated controls).

Close Modal

or Create an Account

Close Modal
Close Modal