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 () and Wen Xie ()
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Xiaojuan Chai: University of Pittsburgh
Yan Guo: University of Pittsburgh
Mengxi Jiang: University of Pittsburgh
Bingfang Hu: University of Pittsburgh
Zhigang Li: Surgical Research, Veterans Affairs Pittsburgh Healthcare System
Jie Fan: Surgical Research, Veterans Affairs Pittsburgh Healthcare System
Meihong Deng: University of Pittsburgh
Timothy R. Billiar: University of Pittsburgh
Heidi R. Kucera: University of California
Nilesh W. Gaikwad: University of California
Meishu Xu: University of Pittsburgh
Peipei Lu: University of Pittsburgh
Jiong Yan: University of Pittsburgh
Haiyan Fu: University of Pittsburgh
Youhua Liu: University of Pittsburgh
Lushan Yu: University of Pittsburgh
Min Huang: Institute of Clinical Pharmacology, Sun Yat-Sen University
Su Zeng: Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University
Wen Xie: University of Pittsburgh

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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-κB dependent and EST is a NF-κB-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.

Date: 2015
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DOI: 10.1038/ncomms8979

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