title: Experimental therapeutics of Nrf2 as a target for prevention of bacterial exacerbations in COPD.
abstract: A growing body of evidence indicates that oxidative stress plays a central role in the progression of chronic obstructive pulmonary disease (COPD). Chronic oxidative stress caused by cigarette smoke generates damage-associated molecular patterns (DAMPs), such as oxidatively or nitrosatively modified proteins and extracellular matrix fragments, which induce abnormal airway inflammation by activating innate and adaptive immune responses. Furthermore, oxidative stress-induced histone deacetylase 2 (HDAC2) inactivity is implicated in amplifying inflammatory responses and corticosteroid resistance in COPD. Oxidative stress also mediates disruption of innate immune defenses, which is associated with acute exacerbation of COPD. Host defense transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates a multifaceted cytoprotective response to counteract oxidative stress-induced pathological injuries. A decrease in Nrf2 signaling is associated with the progression of diseases. Recent evidence indicates that targeting Nrf2 can be a novel therapy to mitigate inflammation, improve innate antibacterial defenses, and restore corticosteroid responses in patients with COPD.
authors.affiliation: Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. sbiswal@jhsph.edu
authors.forename: Shyam
authors.initials: S
authors.lastname: Biswal
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Thimmulappa
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Harvey
mesh_terms: D016503:Drug Delivery Systems; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000517:prevention & control*; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*; D012141:Respiratory Tract Infections / Q000150:complications / Q000517:prevention & control*; D015398:Signal Transduction
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human