Abstract
BackgroundNur77, a key member of the NR4A receptor subfamily, is involved in the regulation of inflammation and immunity. However, the in vivo regulatory roles of Nur77 in sepsis and the mechanisms involved remains largely elusive. In this study, we used Nur77-deficient (Nur77−/−) mice and investigated the function of Nur77 in sepsis.FindingsCompared to wild-type (Nur77+/+) mice, Nur77−/− mice are more susceptible to LPS-induced sepsis and acute liver inflammation. Mechanistically, we observed that Nur77 can interact with TRAF6, a crucial adaptor molecule in the Toll-like receptor-interleukin 1 receptor (TLR-IL-1R) signalling pathway, in in vivo mouse model of sepsis. The interaction may affect TRAF6 auto-ubiquitination, thereby inhibiting NF-κB activation and pro-inflammatory cytokines production.ConclusionsThese in vivo observations reveals an important protective role for Nur77 in LPS-induced sepsis through its regulation to TRAF6 signalling, and highlights the potential clinical application of Nur77 as a molecular target in prevention and/or treatment of sepsis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-016-0112-9) contains supplementary material, which is available to authorized users.
Highlights
Orphan nuclear receptor Nur77 is a member of the NR4A family of nuclear receptors
Our work indicates that Nur77 deficiency in mice increased their susceptibility to LPS-induced sepsis and acute liver injury, and reveal a critical mechanism wherein Nur77 interacts with Tumor necrosis factor receptor associated factor 6 (TRAF6) and regulate its auto-ubiquitination in in vivo mouse model of sepsis
Research suggests that orphan nuclear receptor Nur77 is implicated in inflammation and immunity
Summary
These in vivo observations reveals an important protective role for Nur in LPS-induced sepsis through its regulation to TRAF6 signalling, and highlights the potential clinical application of Nur as a molecular target in prevention and/or treatment of sepsis
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