BPB Reports

Paper Details

BPB Reports
Vol. 4 No. 2 p.59-63 2021
Report
Implication of NF-κB Activation on Ozone-Induced HO-1 Activation
  • Sumihito Togi (Center for Clinical Genomics, Kanazawa Medical University Hospital / Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University / togi@kanazawa-med.ac.jp)
  • Tadashi Matsuda (Graduate School of Pharmaceutical Sciences, Hokkaido University / tmatsuda@pharm.hokudai.ac.jp)
Sumihito Togi 1) 2) , Misa Togi 3) 4) , Satoshi Nagashima 5) , Yuichi Kitai 5) , Ryuta Muromoto 5) , Jun-ichi Kashiwakura 5) , Toshiaki Miura 5) , Tadashi Matsuda 5)
1) Center for Clinical Genomics, Kanazawa Medical University Hospital , 2) Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University , 3) Center for Regenerative Medicine, Kanazawa Medical University Hospital , 4) Department of Regenerative Medicine, Kanazawa Medical University , 5) Graduate School of Pharmaceutical Sciences, Hokkaido University
Received: February 05, 2021;   Accepted: March 09, 2021;   Released: March 25, 2021
Keywords: ozone therapy, oxidative stress, NF-κB signaling, Nrf2 signaling
Abstracts

The controlled and moderate oxidative stress such as ozone induces both inflammatory and anti-inflammatory response. This balance is important for homeostasis of living organisms. Furthermore, it has been shown that this conflict response is mainly regulated by two transcriptional factors, nuclear transcriptional factor κB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). NF-κB is involved in inflammatory responses by regulating expression of cyclooxygenase-2 (COX-2) and various inflammatory cytokines while Nrf2 is involved in anti-inflammatory responses by controlling expression of numerous antioxidant enzymes such as heme oxygenase- 1 (HO-1). We here demonstrate the molecular mechanisms of the crosstalk between NF-κB and Nrf2 activation during the moderate oxidative stress induced by ozone. We first confirmed the activation of NF-κB and Nrf2 signaling during the moderate oxidative stress in HeLa cells. Induction of NF-κB-mediated COX-2 mRNA expression was observed at the early phase after stimulation (30-60 min after ozone treatment). However, induction of HO-1 mRNA expression was observed at the late phase of stimulation (6 h after stimulation). To reveal the crosstalk between NF-κB and Nrf2, we tested whether reduction of NF-κB expression affects ozone-induced Nrf2 activation by knocking down of NF-κB in HeLa cells. Importantly, the HO-1 induction by ozone was remarkably decreased by a reduction in NF-κB expression. These results suggest that the moderate oxidative stress by ozone initially induces NF-κB activation, and this NF-κB activation is required for HO-1 induction at the late phase of the moderate stress.