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

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NF-E2-related factor 2 （Nrf2） regulates the coordinate induction of phase 2 detoxifying and antioxidantenzymes in response to xenobiotics and oxidative stress via antioxidant responsive element. Nrf2 knockout mice arehighly susceptible to the acute toxicity generated by acetaminophen, butylated hydroxytoluene or hyperoxia and tocarcinogenesis induced by benzo[a]pyrene. Recently, it becomes increasingly evident that Nrf2 also plays essential rolesin the protection against infl ammation. Nrf2 regulates the infl ammation during carrageenin-induced pleurisy and lunginfl ammation, wound healing in skin, and dextran sulfate-induced colitis. Nrf2 knockout mice are also susceptible toendotoxin-induced septic shock and allergen-induced asthma. Using carrageenin-induced pleurisy and porcine neutrophilelastase-induced lung injury models, we proposed that this anti-infl ammatory action of Nrf2 relies on the activities inmacrophages. In macrophages, Nrf2 modulates the infl ammatory response by up-regulating a range of anti-oxidative andanti-infl ammatory enzymes, such as CD36 and secretory leukoprotease inhibitor（ SLPI）. CD36 is a macrophage classB 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.
弘前大学の論文