Different roles of ROS and Nrf2 in Cr(VI)-induced inflammatory responses in normal and Cr(VI)-transformed cells

Ram Vinod Roy, Poyil Pratheeshkumar, Yong Ok Son, Lei Wang, John Andrew Hitron, Sasidharan Padmaja Divya, Zhuo Zhang, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Cr(VI) has been associated with adenocarcinomas and squamous cell carcinoma of the lung. The present study shows that acute Cr(VI) treatment in human bronchial epithelial cells (BEAS-2B) increased inflammatory responses (TNF-α, COX-2, and NF-кB/p65) and expression of Nrf2. Cr(VI)-induced generation of reactive oxygen species (ROS) are responsible for increased inflammation. Despite the fact that Nrf2 is a master regulator of response to oxidative stress, silencing of Nrf2 in the acute Cr(VI) treatment had no effect on Cr(VI)-induced inflammation. In contrast, in Cr(VI)-transformed (CrT) cells, Nrf2 is constitutively activated. Knock-down of this protein resulted in decreased inflammation, while silencing of SOD2 and CAT had no effect in the expression of these inflammatory proteins. Results obtained from the knock-down of Nrf2 in CrT cells are very different from the results obtained in the acute Cr(VI) treatment. In BEAS-2B cells, knock-down of Nrf2 had no effect in the inflammation levels, while in CrT cells a decrease in the expression of inflammation markers was observed. These results indicate that before transformation, ROS plays a critical role while Nrf2 not in Cr(VI)-induced inflammation, whereas after transformation (CrT cells), Nrf2 is constitutively activated and this protein maintains inflammation while ROS not. Constitutively high levels of Nrf2 in CrT binds to the promoter regions of COX-2 and TNF-α, leading to increased inflammation. Collectively, our results demonstrate that before cell transformation ROS are important in Cr(VI)-induced inflammation and after transformation a constitutively high level of Nrf2 is important.

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalToxicology and Applied Pharmacology
StatePublished - Sep 15 2016

Bibliographical note

Funding Information:
This research was financially supported by National Institutes of Health (Grant nos. R01ES017244 , R01ES015518 , and R01ES020870 ).

Publisher Copyright:
© 2016


  • Hexavalent chromium
  • Inflammation
  • Nrf2
  • ROS
  • Transformed cells

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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