Meanwhile, the rapid induction of iNOS expression can trigger NO-dependent apoptosis in vitro, which appears to result from DNA damage and may be mediated by a p53-dependent apoptotic pathway [55]. iNOS expression is typically absent in unstimulated cells, but is markedly induced by proinflammatory cytokines including tumor necrosis factor-?? (TNF-??), interleukin (IL)-1, and IL-6 [56, 57].