Sara Staples1, Stephanie B Wall1, Rui Li1, Trent E Tipple2. 1. Neonatal Redox Biology Laboratory, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA. 2. Center for Pregnancy and Newborn Research, Section of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, OK, USA. Electronic address: trent-tipple@ouhsc.edu.
Abstract
AIMS: Interleukin-1β (IL-1β) contributes to the development of bronchopulmonary dysplasia (BPD). Thioredoxin reductase-1 (Txnrd1) inhibition activates nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent responses. Txnrd1 activity is selenium (Se) dependent and Se deficiency is common in prematurity. Auranofin (AFN), a Txnrd1 inhibitor, decreases IL-1β levels and increases Nrf2 activation in lipopolysaccharide (LPS) treated alveolar macrophages. In lung epithelia, AFN-induced Nrf2 activation is Se dependent. We tested the hypothesis that the effects of Txnrd1 inhibition in alveolar macrophages are Se dependent. MAIN METHODS: To establish Se sufficient (Se+) and deficient (Se-) conditions, alveolar (MH-S) macrophages were cultured in 2.5% fetal bovine serum (FBS) ± 25 nM Na2SeO3. Se- (2.5% FBS) and Se+ (2.5% FBS + 25 nM Na2SeO3) cells were cultured in the presence or absence of 0.05 μg/mL LPS and/or 0.5 μM AFN. Nrf2 activation was determined by measuring NADPH quinone oxidoreductase-1 (Nqo1) and glutathione levels. IL-1β mRNA (Il1b) and protein levels were measured using qRT-PCR and ELISA. Data were analyzed by ANOVA followed by Tukey's post-hoc. KEY FINDINGS: We detected an independent effect of AFN, but not LPS, on Nqo1 expression and GSH levels in Se+ and Se- cells. LPS significantly increased Il1b and IL-1β levels in both groups. AFN-mediated attenuation of this effect was not impacted by Se status. SIGNIFICANCE: The beneficial effects of Txnrd1 inhibition in alveolar macrophages are Se-independent and therefore unlikely to be diminished by clinical Se deficiency.
AIMS: Interleukin-1β (IL-1β) contributes to the development of bronchopulmonary dysplasia (BPD). Thioredoxin reductase-1 (Txnrd1) inhibition activates nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent responses. Txnrd1 activity is selenium (Se) dependent and Se deficiency is common in prematurity. Auranofin (AFN), a Txnrd1 inhibitor, decreases IL-1β levels and increases Nrf2 activation in lipopolysaccharide (LPS) treated alveolar macrophages. In lung epithelia, AFN-induced Nrf2 activation is Se dependent. We tested the hypothesis that the effects of Txnrd1 inhibition in alveolar macrophages are Se dependent. MAIN METHODS: To establish Se sufficient (Se+) and deficient (Se-) conditions, alveolar (MH-S) macrophages were cultured in 2.5% fetal bovine serum (FBS) ± 25 nM Na2SeO3. Se- (2.5% FBS) and Se+ (2.5% FBS + 25 nM Na2SeO3) cells were cultured in the presence or absence of 0.05 μg/mL LPS and/or 0.5 μM AFN. Nrf2 activation was determined by measuring NADPH quinone oxidoreductase-1 (Nqo1) and glutathione levels. IL-1β mRNA (Il1b) and protein levels were measured using qRT-PCR and ELISA. Data were analyzed by ANOVA followed by Tukey's post-hoc. KEY FINDINGS: We detected an independent effect of AFN, but not LPS, on Nqo1 expression and GSH levels in Se+ and Se- cells. LPS significantly increased Il1b and IL-1β levels in both groups. AFN-mediated attenuation of this effect was not impacted by Se status. SIGNIFICANCE: The beneficial effects of Txnrd1 inhibition in alveolar macrophages are Se-independent and therefore unlikely to be diminished by clinical Se deficiency.
Authors: Morgan L Locy; Lynette K Rogers; Justin R Prigge; Edward E Schmidt; Elias S J Arnér; Trent E Tipple Journal: Antioxid Redox Signal Date: 2012-06-25 Impact factor: 8.401
Authors: Trent E Tipple; Stephen E Welty; Lynette K Rogers; Thomas N Hansen; Young-Eun Choi; James P Kehrer; Charles V Smith Journal: Am J Respir Cell Mol Biol Date: 2007-06-15 Impact factor: 6.914
Authors: Rodney D Britt; Markus Velten; Morgan L Locy; Lynette K Rogers; Trent E Tipple Journal: Antioxid Redox Signal Date: 2014-02-06 Impact factor: 8.401
Authors: Stephanie B Wall; Rui Li; Brittany Butler; Ashley R Burg; Hubert M Tse; Jennifer L Larson-Casey; A Brent Carter; Clyde J Wright; Lynette K Rogers; Trent E Tipple Journal: Antioxidants (Basel) Date: 2021-04-21
Authors: Fernando Leal-Martínez; Lorena Abarca-Bernal; Alejandra García-Pérez; Dinnaru González-Tolosa; Georgina Cruz-Cázares; Marco Montell-García; Antonio Ibarra Journal: Int J Environ Res Public Health Date: 2022-01-21 Impact factor: 3.390