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-alpha, IL-1 beta, and LPS induced CBR3 expression differentially. While TNF-alpha. (50 ng/ml) or IL-1 beta (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 NF kappa B 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.