The role of Nrf2 in the protection against infl ammation and innate immunity

NF-E2-related factor 2 （Nrf2） regulates the coordinate induction of phase 2 detoxifying and antioxidant enzymes in response to xenobiotics and oxidative stress via antioxidant responsive element. Nrf2 knockout mice are highly susceptible to the acute toxicity generated by acetaminophen, butylated hydroxytoluene or hyperoxia and to carcinogenesis induced by benzo[a]pyrene. Recently, it becomes increasingly evident that Nrf2 also plays essential roles in the protection against infl ammation. Nrf2 regulates the infl ammation during carrageenin-induced pleurisy and lung infl ammation, wound healing in skin, and dextran sulfate-induced colitis. Nrf2 knockout mice are also susceptible to endotoxin-induced septic shock and allergen-induced asthma. Using carrageenin-induced pleurisy and porcine neutrophil elastase-induced lung injury models, we proposed that this anti-infl ammatory action of Nrf2 relies on the activities in macrophages. In macrophages, Nrf2 modulates the infl ammatory response by up-regulating a range of anti-oxidative and anti-infl ammatory enzymes, such as CD36 and secretory leukoprotease inhibitor（ SLPI）. CD36 is a macrophage class B scavenger receptor involved in the uptake of apoptotic neutrophils and microorganisms such as Staphylococcus aureus. Thus, Nrf2 may play important roles in the protection of infl ammation and innate immune response