TABLE 1

Studies focused on the role of Nrf2 in allergic airway and asthma

Disease ModelEnvironmental Factors/ActivatorsGenetic ModelEffect of Knockout/Knockdown (Nrf2 or Keap1)References
OVA-induced allergic airway inflammation/asthmaCD1: ICRWT & Nrf2(−/−)↑ AHR, ↑ inflammatory cell infiltrate in lung, ↑ lipid peroxidation, ↑ IL-4, IL-13, ↑ mucus cell metaplasia(Rangasamy et al., 2005)
DieselC57BL/6WT & Nrf2(−/−)↑ AHR, ↑ inflammatory cells infiltrate in lung, ↑ IL-5, ↑ mucus cell hyperplasia(Li et al., 2010)
ambient UFP (<0.18 μm)BALB/c WT & Nrf2(−/−), DC from WT & Nrf2(−/−)↑ Adjuvant effect of intranasally instilled UFP, ↑ eosinophil count and IL-13 in BAL, V serum IgG1(Li et al., 2013)
Tam-Keap1−/−↓ AHR, ↓ eosinophilic inflammation, and ↓ IL-4 and IL-13 in BAL(Sussan et al., 2015)
Ragweed Extract-induced asthmaBMDC and lung DC from WT Nrf2 (−/−)↑ CD80, CD86, and MHCII on DC, ↑ IL-6 and TNF-α(Rangasamy et al., 2010)
Cl2-induced inflammation and airway hyperresponsivenessBALB/cWT & Nrf2(−/−)↓ mRNA for antioxidant genes (NQO1 and GPX2)(Ano et al., 2017)
IL-33-induced allergic lung inflammationCDDO-Im, 15d-PGJ2C57BL/6WT & Nrf2(−/−)Transient ↑ in IL-33, ↑ ILC2 proliferation(Nagashima et al., 2019)
PM2.5-induced airway inflammationC57BL/6WT & Nrf2(−/−)↓ Inflammatory infiltrate, ↓ oxidative stress, ↓ lung injury, ↓ CYP2E1(Ding et al., 2021)
C57BL/6WT & Nrf2(−/−)↑ Lung function, ↓ alveolar wall thickening, ↓ in low-grade inflammation(Jiang et al., 2021)
  • CDDO-Im, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole; GPX2, glutathione peroxidase 2; ILC2, type 2 innate lymphoid cells; 15d-PGJ2, 15-deoxy-prostaglandin J2.