Oestrogen sulfotransferase ablation sensitizes mice to sepsis

Xiaojuan Chai, Yan Guo, Mengxi Jiang, Bingfang Hu, Zhigang Li, Jie Fan, Meihong Deng, Timothy R. Billiar, Heidi R. Kucera, Nilesh W. Gaikwad, Meishu Xu, Peipei Lu, Jiong Yan, Haiyan Fu, Youhua Liu, Lushan Yu, Min Huang, Su Zeng, Wen Xie

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Sepsis is the host's deleterious systemic inflammatory response to microbial infections. Here we report an essential role for the oestrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the caecal ligation and puncture (CLP) and lipopolysaccharide models of sepsis induce the expression of EST and compromise the activity of oestrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised oestrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes oestrogen deactivation and sensitizes mice to CLP-induced inflammatory response. The induction of EST by sepsis is NF-κ B dependent and EST is a NF-κ B-target gene. The reciprocal regulation of inflammation and EST may represent a yet-to-be-explored mechanism of endocrine regulation of inflammation, which has an impact on the clinical outcome of sepsis.

Original languageEnglish (US)
Article number8979
JournalNature Communications
Volume6
DOIs
StatePublished - Aug 10 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Chai, X., Guo, Y., Jiang, M., Hu, B., Li, Z., Fan, J., Deng, M., Billiar, T. R., Kucera, H. R., Gaikwad, N. W., Xu, M., Lu, P., Yan, J., Fu, H., Liu, Y., Yu, L., Huang, M., Zeng, S., & Xie, W. (2015). Oestrogen sulfotransferase ablation sensitizes mice to sepsis. Nature Communications, 6, [8979]. https://doi.org/10.1038/ncomms8979