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Depletion of Nrf2 Enhances Inflammation Induced by Oxyhemoglobin in Cultured Mice Astrocytes

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Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element pathway has been proved to be the key regulator in reducing inflammatory damage, which is involved in subarachnoid hemorrhage (SAH). Here, in a traditional in vitro SAH model, we investigated the effect of Nrf2 depletion on pro-inflammatory cytokines production. Primary cultured astrocytes from Nrf2 wild type (WT) or knockout (KO) mouse were exposed or not exposed to oxyhemoglobin (OxyHb). Then the DNA-binding activity of transcription factor nuclear factor-κB (NF-κB) was detected by EMSA. The expression of TNF-α, IL-1β, IL-6 and MMP9 were evaluated. The activity of MMP9 was measured by Gelatin zymography. After exposure to OxyHb, NF-κB was activated and the expression of downstream pro-inflammatory cytokines was up-regulated in astrocytes. And such up-regulation was much higher in KO astrocytes than in WT astrocytes, which means more aggravated inflammation in Nrf2 deficient astrocytes. These results suggest that astrocytes participate in inflammatory process after SAH and the absence of Nrf2 may induce more aggressive inflammation through activation of NF-κB pathway.

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Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (No. 81070974), the Jiangsu Provincial Key Subject (X4200722), and Jinling Hospital of Nanjing, China (2010Q017).

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There is no competing interest.

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Authors and Affiliations

  1. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People’s Republic of China

    Hao Pan, Handong Wang, Lin Zhu, Lei Mao, Liang Qiao & Xingfen Su

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  1. Hao Pan
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  2. Handong Wang
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  3. Lin Zhu
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  4. Lei Mao
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Correspondence to Handong Wang.

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Pan, H., Wang, H., Zhu, L. et al. Depletion of Nrf2 Enhances Inflammation Induced by Oxyhemoglobin in Cultured Mice Astrocytes. Neurochem Res 36, 2434–2441 (2011). https://doi.org/10.1007/s11064-011-0571-6

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  • DOI: https://doi.org/10.1007/s11064-011-0571-6

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