Premium
Luteolin protects human glomerular endothelial cells from TNF‐α‐induced endothelial dysfunction by attenuating ET‐1 and ROS production
Author(s) -
Yang Weiwei,
Bradshaw Jessica,
Bakrania Bhavisha,
Duncan Jeremy,
Satchell Simon,
Spradley Frank,
Granger Joey,
Rana Sarosh
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.865.9
Subject(s) - luteolin , endothelial dysfunction , tumor necrosis factor alpha , preeclampsia , reactive oxygen species , medicine , oxidative stress , endothelial stem cell , endocrinology , pharmacology , andrology , chemistry , pregnancy , biology , biochemistry , in vitro , antioxidant , genetics , quercetin
Preeclampsia (PE) is a pregnancy‐specific syndrome that affects 5~8% pregnancies and is a leading causes of maternal and neonatal morbidity and mortality, especially in low‐income and middle‐income countries. Although the underlying mechanism remains unclear, PE is associated with maternal endothelial dysfunction characterized by elevated endothelin (ET‐1) and reactive oxygen species (ROS). Tumor necrosis factor‐α (TNF‐α) has been reported as one of the regulators of endothelial dysfunction and this inflammatory factor is elevated significantly in the placenta of patients with PE. Recently, luteolin has drawn wide scientific attention due to a number of health benefits and reduced risk of several diseases, including hypertension and cardiovascular disease. However, whether luteolin might have therapeutic potential in PE is unknown. We tested the hypothesis that luteolin protects endothelial cells against TNF‐α by reducing ET‐1 and ROS production. We pretreated immortalized human glomerular endothelial cells (hGEnCs) with luteolin for 1 hour before recombinant human TNF‐α exposure. We found that exposure of hGEnCs to TNF‐α for 24 h significantly increased the release of ET‐1 by 1.9 fold (3.10±0.70 pg/mL vs 1.07±0.20 pg/mL, p <0.05). Pretreatment with luteolin significantly attenuated TNF‐α‐induced ET‐1 release in a dose‐dependent manner, in particular, 20μM luteolin completely attenuated the effect of TNF‐α on ET‐1 production (3.10±0.70 pg/mL vs 0.56±0.08 pg/mL, p <0.01). We further utilized 2',7'‐dichlorodihydrofluorescein diacetate (H2DCFDA) assay to assess whether luteolin has the potential to prevent TNF‐α‐induced ROS in hGEnCs. We found that luteolin significantly ameliorated the effect of TNF‐α on ROS generation. Pretreatment with luteolin at physiologically relevant concentrations (2 μM) significantly decreased TNF‐α‐induced ROS production within cells (fluorescent intensity: 1795±89.26 vs 1237±98.29, p <0.01), while at 20μM luteolin, TNF‐α‐induced ROS was markedly inhibited by 66% (fluorescent intensity: 1795±89.26 vs 618.5±40.81, p <0.01). Taken together, our preliminary data suggest that luteolin significantly attenuates TNF‐α‐induced ET‐1 release and ROS generation. Support or Funding Information 81601318, P01HL051971, P20GM104357, T32HL105324, 18POST33990293, HL130577 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .