NO-releasing NSAIDs are caspase inhibitors

Nitrosation of thiol-containing proteins is a mechanism for cell regulation. Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemical entities obtained by adding a nitroxybutyl moiety to a conventional NSAID. NO-NSAIDs inhibit inflammation via cyclo-oxygenase (COX)-dependent and -independent effects. Similarly to endogenous NO, NO-NSAIDs are potent inhibitors of T helper1 (Th1) type cytokines. This effect is largely owing to post-translational nitrosation and therefore inactivation of cysteine proteases, such as the interleukin (IL)-1β converting enzyme (ICE/caspase-1) involved in pro-cytokine processing.