Curcumin relieves paraquat‑induced lung injury through inhibiting the thioredoxin interacting protein/NLR pyrin domain containing 3‑mediated inflammatory pathway

Ren,Yi; Yang,Zhizhou; Sun,Zhaorui; Zhang,Wei; Chen,Xin; Nie,Shinan

doi:10.3892/mmr.2019.10612

Curcumin relieves paraquat‑induced lung injury through inhibiting the thioredoxin interacting protein/NLR pyrin domain containing 3‑mediated inflammatory pathway

Authors:
- Yi Ren
- Zhizhou Yang
- Zhaorui Sun
- Wei Zhang
- Xin Chen
- Shinan Nie
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Affiliations: Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
Published online on: August 23, 2019 https://doi.org/10.3892/mmr.2019.10612
Pages: 5032-5040
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

When paraquat (PQ) enters the human body, it increases oxidative stress and inflammation, ultimately resulting in acute lung injury (ALI). Curcumin, a naturally occurring compound, has been reported to ameliorate PQ‑induced ALI; however, the underlying molecular mechanisms remain unclear. In the present study, normal lung fibroblasts (WI‑38VA13) were treated with 10 µmol/l PQ for 48 h, followed by a further 48 h incubation with 300 µmol/l curcumin. Cells were then harvested to determine their viability. Flow cytometry was performed to analyze the levels of reactive oxygen species (ROS) and the rate of apoptosis. The levels of apoptotic proteins and activation of the thioredoxin interacting protein/NLR pyrin domain containing 3 (TXNIP/NLRP3) axis were measured via reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Proinflammatory cytokine levels were examined using enzyme‑linked immunosorbent assays. Finally, the expression levels of Notch1, extracellular signal‑regulated kinase 1/2 (ERK1/2) and phosphorylated‑ERK1/2 were evaluated via western blotting. Following treatment with curcumin, PQ‑induced increases in ROS levels and apoptosis were significantly attenuated, and Bcl‑2 expression levels were upregulated, whereas those of Bax were downregulated. It was also observed that curcumin treatment downregulated the expression levels of TXNIP, NLRP3, interleukin (IL)‑1β and IL‑18, and downstream caspase‑1 compared with PQ treatment alone. Curcumin significantly attenuated the upregulation of Notch1 without affecting ERK1/2 phosphorylation. The present findings suggested that the inhibitory effects of curcumin on TXINP1 may inhibit activation of the NLRP3 inflammasome, subsequently suppressing the upregulation of proinflammatory cytokines and ultimately improving PQ‑induced ALI.

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