Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils

• Published in: Antioxidants & redox signaling Vol. 9; no. 11; p. 1963
• Main Authors: Thimmulappa, Rajesh K, Fuchs, Ralph J, Malhotra, Deepti, Scollick, Catherine, Traore, Kassim, Bream, Jay H, Trush, Michael A, Liby, Karen T, Sporn, Michael B, Kensler, Thomas W, Biswal, Shyam
• Format: Journal Article
• Language: English
• Published: United States 01.11.2007
• Subjects: Cytokines - metabolism; Drug Evaluation, Preclinical; Gene Expression Regulation - drug effects; Humans; Imidazoles - pharmacology; Inflammation - chemically induced; Inflammation - genetics; Inflammation - immunology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lipopolysaccharides - toxicity; Neutrophils - drug effects; Neutrophils - immunology; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - physiology; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - pharmacology; Reactive Oxygen Species - metabolism; Receptors, Formyl Peptide - metabolism; RNA, Messenger - metabolism; Time Factors; Tumor Necrosis Factor-alpha - metabolism

Sepsis is characterized by an inappropriate host immune-inflammatory response and sustained oxidative damage. Nrf2, a bZIP oxidant-responsive transcription factor, regulates a battery of cytoprotective genes including antioxidants and maintains cellular redox homeostasis. Mouse studies have demonstr...