STAT5a induces endotoxin tolerance by alleviating pyroptosis in kupffer cells

Tao Wang; Hua Zhong; Wenfeng Zhang; Jian Wen; Zhujun Yi; Peizhi Li; Jianping Gong

doi:10.1016/j.molimm.2020.03.016

STAT5a induces endotoxin tolerance by alleviating pyroptosis in kupffer cells

Mol Immunol. 2020 Apr 13:122:28-37. doi: 10.1016/j.molimm.2020.03.016. Online ahead of print.

Authors

Tao Wang¹, Hua Zhong², Wenfeng Zhang¹, Jian Wen³, Zhujun Yi¹, Peizhi Li¹, Jianping Gong⁴

Affiliations

¹ Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
² Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, 400010, China.
³ Department of Hepatobiliary Surgery, the Affiliated Hospital of Southwest Medical University, 646000, China.
⁴ Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. Electronic address: gongjianping@cqmu.edu.cn.

PMID: 32298872
DOI: 10.1016/j.molimm.2020.03.016

Abstract

Pyroptosis, a newly discovered type of programmed cell death, affects endotoxin tolerance in macrophages. However, the factors acting on the nod-like receptor 3 (Nlrp3) inflammasome and caspase1 activation to impede pyroptosis and resulting in tolerance and survival in sepsis were needed to discovered. Here, we found that signal transducer and activator of transcription 5A (STAT5a) restrains pyroptosis in Kupffer cells (KCs) and induces endotoxin tolerance (ET) in a sepsis model. The lentiviral knockdown of STAT5a led to enhanced pyroptosis in KCs, increased IL-1β production and decreased IL-10 production via intricate NF-κb signaling regulation. Thus, our findings reveal a novel mechanism of STAT5a-midiated endotoxin tolerance in KCs.

Keywords: Endotoxin tolerance; Kupffer cells; NF-κ b; Pyroptosis; STAT5a.