Down-Regulated Receptor Interacting Protein 140 Is Involved in Lipopolysaccharide-Preconditioning-Induced Inactivation of Kupffer Cells and Attenuation of Hepatic Ischemia Reperfusion Injury

Abstract

BackgroundLipopolysaccharide (LPS) preconditioning is known to attenuate hepatic ischemia/reperfusion injury (I/RI); however, the precise mechanism remains unclear. This study investigated the role of receptor-interacting protein 140 (RIP140) on the protective effect of LPS preconditioning in hepatic I/RI involving Kupffer cells (KCs).MethodsSprague—Dawley rats underwent 70% hepatic ischemia for 90 minutes. LPS (100 μg/kg) was injected intraperitoneally 24 hours before ischemia. Hepatic injury was observed using serum and liver samples. The LPS/NF-κB (nuclear factor-κB) pathway and hepatic RIP140 expression in isolated KCs were investigated.ResultsLPS preconditioning significantly inhibited hepatic RIP140 expression, NF-κB activation, and serum proinflammatory cytokine expression after I/RI, with an observation of remarkably reduced serum enzyme levels and histopathologic scores. Our experiments showed that protection effects could be effectively induced in KCs by LPS preconditioning, but couldn’t when RIP140 was overexpressed in KCs. Conversely, even without LPS preconditioning, protective effects were found in KCs if RIP140 expression was suppressed with siRNA.ConclusionsDown-regulated RIP140 is involved in LPS-induced inactivation of KCs and hepatic I/RI attenuation.

Macrophage Regnase-1 Deletion Deteriorates Liver Ischemia/Reperfusion Injury Through Regulation of Macrophage Polarization

“…Later, outcomes with macrophage destruction and reconstitution conducted sequentially proved that macrophages are particularly responsible for the I/R-derived damage. In fact, numerous articles have already highlighted the specific role of macrophages in liver I/R, consistent with our findings (Yuan et al, 2016).…”

Age over sex: evaluating gut microbiota differences in healthy Chinese populations

“…The underlying reasons and implications warrant further investigation. Previous studies report that small amounts of LPS can induce endotoxin tolerance (Yuan et al, 2016), which may explain the protective effects of increased LPS-producing bacteria in elderly people. Moreover, alterations in the gut environment that align with aging, such as pH shifts and alterations in gut motility, can favor the growth of different bacterial populations (Kedia et al, 2018), including those that produce LPS.…”

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“…The underlying reasons and implications warrant further investigation. Previous studies report that small amounts of LPS can induce endotoxin tolerance (Yuan et al, 2016), which may explain the protective effects of increased LPS-producing bacteria in elderly people. Moreover, alterations in the gut environment that align with aging, such as pH shifts and alterations in gut motility, can favor the growth of different bacterial populations (Kedia et al, 2018), including those that produce LPS.…”