Phoenixin-20 Ameliorates Lipopolysaccharide-Induced Activation of Microglial NLRP3 Inflammasome
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ORIGINAL ARTICLE
Phoenixin-20 Ameliorates Lipopolysaccharide-Induced Activation of Microglial NLRP3 Inflammasome Xiangliang Zeng 1 & Yanchun Li 1 & Sicong Ma 1 & Yidan Tang 1 & Hanwen Li 1 Received: 18 January 2020 / Revised: 11 May 2020 / Accepted: 13 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Injury associated with neuroinflammation has been linked with several kinds of neurodegenerative diseases. The activation of the NLRP3 inflammasome plays an important role in microglia-mediated inflammation. Phoenixin (PNX)-20 is a newly discovered neuropeptide with pleiotropic effects involved in the regulation of reproductive and cognitive function, depression, and food uptake. This study investigated whether PNX-20 possesses a protective effect against lipopolysaccharide (LPS)-induced activation of the NLRP3 inflammasome in microglia. Firstly, our results show that the PNX-20 treatment significantly prevented LPSinduced expression of NADPH oxidase 4 (NOX-4) and the generation of reactive oxygen species (ROS). Secondly, PNX-20 mitigated LPS-induced upregulation of TxNIP, an upstream regulator of NLRP3 inflammasome activation. Thirdly, further evaluation of the major components of the NLRP3 inflammasome revealed that PNX-20 inhibited LPS-mediated upregulation of NLRP3, ASC, and cleaved caspase-1 (P10). Notably, based on our results, the inhibitory effect of PNX-20 on the NLRP3 inflammasome results in the inhibition of IL-1β and IL-18 secretions. Finally, we found that PNX-20 ameliorated the reduction in SIRT1 expression induced by LPS. When microglial SIRT1 was inhibited by nicotine, PNX-20 lost its suppressive effect on the expression of NLRP3, ASC, and caspase-1, as well as the secretion of IL-1β and IL-18. As a result of these findings, we draw the conclusion that the neuroprotective effect of PNX-20 is dependent on SIRT1. Collectively, the study shows that PNX-20 has a regulatory effect via modulation of neuroinflammation. Keywords Neuroinflammation . Phoenixin 20 . Microglia . NLRP3 inflammasome . SIRT1
Introduction Human central nerve tissues are guarded by a highly selective blood–brain barrier (BBB) to prevent the entry of any harmful substances and/or peripheral immune cells. The neuroimmune system is regulated by the cell types of which it is comprised—mainly microglia and astrocytes (Streit and Kincaid-Colton 1995). Microglia constitute the innate immune system of the central nervous system (CNS) and are the most important contributors to the neuroinflammatory response. Microglia are ubiquitously distributed in most parts of the CNS and account for 10–15% of all cells in the brain
* Yanchun Li [email protected] 1
Department of Neurology, First Affiliated Hospital, Hunan University of Medicine, Huaihua, No.225, Yushi Road, Hecheng District, Huaihua City 418000, Hunan Province, China
(Xavier et al. 2014). The function of microglia is similar to that of the resident macrophage cells in the peripheral immune system, acting as the first line of defense in the CNS. I
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