Selenium-independent antioxidant and anti-inflammatory effects of thioredoxin reductase inhibition in alveolar macrophages

LIFE SCIENCES

卷:259

Article

Staples, Sara¹  Wall, Stephanie B.¹  Li, Rui¹  Tipple, Trent E.² 

[1] Univ Alabama Birmingham, Dept Pediat, Neonatal Redox Biol Lab, Birmingham, AL USA

[2] Univ Oklahoma, Ctr Pregnancy & Newborn Res, Dept Pediat, Sect Neonatal Perinatal Med,Coll Med, Oklahoma City, OK 73104 USA

关键词: Auranofin;    Thioredoxin;    Thioredoxin reductase;    Selenium;    Prematurity;    Macrophage;    Interleukin-1 beta;   

DOI  :  10.1016/j.lfs.2020.118285

来源: Elsevier

【 摘 要 】

Aims: Interleukin-1 beta (IL-1 beta) 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-1 beta 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 mu g/mL LPS and/or 0.5 mu M AFN. Nrf2 activation was determined by measuring NADPH quinone oxidoreductase-1 (Nqo1) and glutathione levels. IL-1 beta 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-1 beta 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.

【 授权许可】

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