Fig. 9

Schematic of NOX2 regulation of macrophage activation. Activation of TLR4 initiates a signaling cascade that leads to activation of NOX2 and increased ROS production; this in turn induces the activation of STAT1, which leads to an increase in the production of pro-inflammatory mediators. TLR4 signaling also induces the production of IL-10, which acts in autocrine fashion to regulate TLR4-induced changes. In NOX2^−/− cells, TLR4-induced changes are significantly different; NOX2-deficiency is associated with a decrease in pro-inflammatory markers and significantly greater IL-10 production. This increase in IL-10 leads to a robust increase in STAT3 signaling, which in conjunction with STAT6 activation, leads to increased expression of anti-inflammatory markers