Nrf2-deficient female mice develop lupus-like autoimmune nephritis11See Editorial by Byrd and Thomas, p. 1606.

Abstract

These data indicate that the aged Nrf2-deficient female mice develop lupus-like autoimmune nephritis and suggest that nrf2 is one of the genes determining susceptibility to autoimmune disease. Analysis of nephritis in the Nrf2-deficient female mouse may clarify the mechanisms leading to the development of lupus disease.

Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels

“…Enomoto et al (2001) and Chan et al (2001) clearly demonstrated an enhanced susceptibility to acetaminophen in Nrf2-deficient mice. We also reported that Nrf2 female mice developed autoimmune glomerulonephritis probably due to susceptibility to oxidative stress (Yoh et al, 2001). In addition, Ramos-Gomez et al (2001) showed that Nrf2 was central to the constitutive and inducible expression of phase two enzymes in vivo and dramatically influences susceptibility to carcinogens.…”

Activation of the Nrf2/antioxidant response pathway increases IL-8 expression

“…Female Nrf2-deficient mice develop a lupus-like immune-complex disease as they age, characterized by anti-nuclear autoantibodies and glomerulonephritis [9,10]. In these models, Nrf2-deficient animals show increased indices of oxidant stress, decreased antioxidant capacity, and less activation of antioxidant genes than Nrf2-intact mice [5,6,[9][10][11]. Taken together, these data suggest that Nrf2-dependent genes play a role in suppressing inflammation and maintaining immune tolerance.…”

“…Mice deficient in Nrf2 display significantly more pulmonary inflammation in hyperoxic and bleomycin-induced lung injury compared to wild-type animals [5,6], and demonstrate prolonged inflammation during cutaneous wound healing [7] and carrageenan-induced pleurisy [8]. Female Nrf2-deficient mice develop a lupus-like immune-complex disease as they age, characterized by anti-nuclear autoantibodies and glomerulonephritis [9,10]. In these models, Nrf2-deficient animals show increased indices of oxidant stress, decreased antioxidant capacity, and less activation of antioxidant genes than Nrf2-intact mice [5,6,[9][10][11].…”

Evidence that Cisplatin-induced Auditory Damage is Attenuated by Downregulation of Pro-inflammatory Cytokines Via Nrf2/HO-1

“…In addition to its role in regulating ROS levels, several recent studies have showed that the Nrf2 pathway regulates immune and inflammatory processes. Yoh et al (2001) reported that Nrf2-deficient female mice developed lupus-like autoimmune nephritis. It was also demonstrated that Nrf2-deficient mice exhibit prolonged inflammation during cutaneous wound healing and display enhanced bronchial inflammation and susceptibility to cigarette smoke-induced emphysema (Iizuka et al 2005).…”