Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription
Eri H. Kobayashi,Takafumi Suzuki,Ryo Funayama,Takeshi Nagashima,Makiko Hayashi,Hiroki Sekine,Nobuyuki Tanaka,Takashi Moriguchi,Hozumi Motohashi,Keiko Nakayama,Masayuki Yamamoto +10 more
TL;DR: It is demonstrated that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β, and establishes a molecular basis for an NRF2-mediated anti-inflammation approach.
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Abstract: Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. Chromatin immunoprecipitation (ChIP)-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2-binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach.
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Citations
Simvastatin-Mediated Nrf2 Activation Induces Fetal Hemoglobin and Antioxidant Enzyme Expression to Ameliorate the Phenotype of Sickle Cell Disease
Caixia Xi,Colathur K. Palani,Mayuko Takezaki,Huidong Shi,Anatolij Horuzsko,Betty S. Pace,Xingguo Zhu +6 more
- 02 Feb 2024
TL;DR: Simvastatin-mediated Nrf2 activation induces fetal hemoglobin and antioxidant enzyme expression to ameliorate the phenotype of sickle cell disease.
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Med1 inhibits ferroptosis and alleviates liver injury in acute liver failure via Nrf2 activation
Zi-Ying Lei,Zhi-Hui Li,Jing Cao,Junfeng Chen,Shi-Bo Meng,Jia-Lei Wang,Jing Zhang,Bing-Liang Lin +7 more
TL;DR: Findings indicate that Med1 suppresses ferroptosis and alleviates liver injury in LPS/D-GalN-induced ALF through the activation of Nrf2, and substantiate the therapeutic viability of targeting the Med1-Nrf2 axis as a means of treating individuals afflicted with ALF.
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The alleviative effect of flavonol‐type Nrf2 activator rhamnazin from Physalis alkekengi L. var. franchetii (Mast.) Makino on pulmonary disorders
Xuewei Wu,Tian-Tian Wang,Hui-Xin Hu,Kan Zhang,Yu Zhao,Bao-Bing Zhao,Hong Lu,Xiaoming Wang,Tao Shen +8 more
TL;DR: Data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF‐κB activation and promoting autophagy.
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A Critical Review on the Potency of Phytoconstituents in the Management of COVID-19
Kannan Raman,Kalirajan Rajagopal,Gomathi Swaminathan,Srikanth Jupudi,Kuldeep Dhama,Ranadhir Barua,Talha Bin Emran,Hamid Osman,Mayeen Uddin Khandaker +8 more
TL;DR: Phytoconstituents have shown promise in treating viral diseases and have the potential to be used against SARS-CoV-2. They act through various mechanisms, including protease inhibition, spike protein inhibition, and Nrf2 inhibition. Natural products are safe, stable, and dependable source for finding drugs to control the current pandemic.
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