Induction of an Inflammatory Loop by Interleukin-1β and Tumor Necrosis Factor-α Involves NF-kB and STAT-1 in Differentiated Human Neuroprogenitor Cells
Figure 7
Cytokine-mediated induction of CXCL10 promoter requires NF-kB and STAT-1.
A. Differentiated NPCs transfected with wild type CXCL10 promoter were preincubated in the presence of 10 µM of Bay 11-7085, NF-kB inhibitor or 1 µM of JAK inhibitor to block STAT-1 activation, followed by exposure to 2 ng/ml each of IL-1β and TNF-α for 18 h. B. Cells were transfected with wild type, and mutant promoter constructs and cultured in the presence of 2 ng/ml each of IL-1β, TNF-α or both for 18 h. Treated cells (A and B) were processed for the assay of luciferases. Inhibition of NF-kB or STAT-1 resulted in significant decreases in cytokine-mediated promoter activation. Mutation of ISRE or kB elements led to loss of synergy between IL-1β and TNF-α. *P<0.01; **P<0.001 compared to untreated control. #P<0.01 vs cells treated with cytokines in the absence of inhibitors (A) or cells transfected with wild type promoter (B).