title: Expression of human carbonyl reductase 3 (CBR3; SDR21C2) is inducible by pro-inflammatory stimuli.
abstract: Until today, the physiologic role of human carbonyl reductase 3 (CBR3; SDR21C2), a member of the short-chain dehydrogenase/reductase superfamily remains obscure. Since the transcriptional regulation is closely related to the function of a protein, elucidation of the regulation of CBR3 should help to understand its physiologic role. We recently identified CBR3 as a novel target gene of Nrf2, a cellular sensor of oxidative stress. In this study, we provide for the first time evidence that pro-inflammatory stimuli induce the expression of the CBR3 gene. Treatment of human cancer cells HT-29 (colon) and HepG2 (liver) with TNF-α, IL-1β, and LPS induced CBR3 expression differentially. While TNF-α (50 ng/ml) or IL-1β (1 and 10 ng/ml), induced CBR3 mRNA expression in HT-29 cells (up to 10-fold) and HepG2 cells (up to 20-fold), LPS activated the CBR3 gene only in HepG2 cells. Furthermore, overexpression of the NFκB subunits p65 and p50 alone or in combination elevated CBR3 mRNA levels (3.9-fold) in HT-29 cells. According to our results, CBR3 is a novel target gene of inflammatory stimuli, and elucidation of its detailed role in inflammation deserves further investigation.
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Malátková
authors.forename: Bettina
authors.initials: B
authors.lastname: Ebert
authors.forename: Vladimír
authors.initials: V
authors.lastname: Wsól
authors.forename: Edmund
authors.initials: E
authors.lastname: Maser
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000429:Alcohol Oxidoreductases; C531130:CBR3 protein, human