Indispensable role of β-arrestin2 in the protection of remifentanil preconditioning against hepatic ischemic reperfusion injury.

Abstract

Our previous study demonstrated that remifentanil, an opioid agonist, conferred profound liver protection during hepatic ischemia reperfusion injury (HIRI), in which Toll-like receptors (TLRs) played a crucial role in mediating the inflammatory responses. β-arrestin2, a well-known mu opioid receptor desensitizer, is also a negatively regulator of Toll-like receptor 4 (TLR4)-mediated inflammatory reactions in a mitogen-activated protein kinase (MAPK)-dependent manner. Using the rodent models of hepatic ischemia reperfusion injury both in wild type and TLR4 knockout (TLR4 KO) mice, we found that remifentanil preconditioning could inhibit the expression of TLR4 and reduce the inflammatory response induced by HIRI in wild type but not in TLR4 KO mice. For the in-vitro study, LPS was used to treat RAW264.7 macrophage cells to mimic the inflammatory response induced by HIRI. Remifentanil increased β-arrestin2 expression both in vivo and in vitro, while after silencing β-arrestin2 RNA, the effect of remifentanil in reducing cell death and apoptosis, as well as decreasing phosphorylation of ERK and JNK were abolished in RAW264.7 cells. These data suggested that remifentanil could ameliorate mice HIRI through upregulating β-arrestin2 expression, which may function as a key molecule in bridging opioid receptor and TLR4 pathway.

• Authors: Yuting Yang, Caiyang Chen, Cui Cui, Yingfu Jiao, Peiying Li, Ling Zhu, Weifeng Yu, Qiang Xia, Daxiang Wen, Liqun Yang
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 2087 (02 14 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 30765766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Opioid, mu
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• beta-Arrestin 2
• beta-Arrestins
• Remifentanil

Topics

• Animals
• Apoptosis (drug effects)
• Ischemic Preconditioning (methods)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• RAW 264.7 Cells
• Receptors, Opioid, mu (metabolism)
• Remifentanil (metabolism, pharmacology)
• Reperfusion Injury (drug therapy)
• Toll-Like Receptor 4 (genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• beta-Arrestin 2 (metabolism, physiology)
• beta-Arrestins (metabolism, physiology)