Diphenyleneiodium Chloride Blocks Inflammatory Cytokine- Induced Up-Regulation of Group IIA Phospholipase A2 in Rat

Inflammatory cytokines, interleukin 1b and tumor necrosis fac-tor-a, potently stimulate rat mesangial cells to express and secrete group IIA phospholipase A2 (PLA2). Cytokine-induced up-regulation of PLA2 has been blocked by inhibitors (antioxi-dants) of the transcription factor, nuclear factor-kB (NF-kB), suggesting a role for NF-kB in the regulation of group IIA PLA2 expression. Reactive oxygen species such as H2O2, which are elevated in mesangial cells after cytokine activation, can mimic cytokine-induced NF-kB activation. However, the source of reactive oxygen species generation in mesangial cells, pro-duced by cytokine stimulation, has yet to be clarified. Recently, tumor necrosis factor-a has been demonstrated to increase superoxide radical generation in mesangial cells. Therefore, we hypothesized that a selective NADPH oxidase inhibitor, diphe