The natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation

Chronic inflammation is characterized by persisting leukocyte infiltration of the affected tissue, which is enabled by activated endothelial cells (ECs). Chronic inflammatory diseases remain a major pharmacotherapeutic challenge, and thus the search for novel drugs and drug targets is an ongoing dem...

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Autores principales:	Luisa D. Burgers, Betty Luong, Yanfen Li, Matthias P. Fabritius, Stylianos Michalakis, Christoph A. Reichel, Rolf Müller, Robert Fürst
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Vioprolide A Natural product Endothelial cells Inflammation Protein synthesis Nucleolar protein 14 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4d20bc27720141d9918bfdcaca1d4432
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spelling	oai:doaj.org-article:4d20bc27720141d9918bfdcaca1d44322021-11-14T04:28:53ZThe natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation0753-332210.1016/j.biopha.2021.112255https://doaj.org/article/4d20bc27720141d9918bfdcaca1d44322021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010398https://doaj.org/toc/0753-3322Chronic inflammation is characterized by persisting leukocyte infiltration of the affected tissue, which is enabled by activated endothelial cells (ECs). Chronic inflammatory diseases remain a major pharmacotherapeutic challenge, and thus the search for novel drugs and drug targets is an ongoing demand. We have identified the natural product vioprolide A (vioA) to exert anti-inflammatory actions in vivo and in ECs in vitro through inhibition of its cellular target nucleolar protein 14 (NOP14). VioA attenuated the infiltration of microglia and macrophages during laser-induced murine choroidal neovascularization and the leukocyte trafficking through the vascular endothelium in the murine cremaster muscle. Mechanistic studies revealed that vioA downregulates EC adhesion molecules and the tumor necrosis factor receptor (TNFR) 1 by decreasing the de novo protein synthesis in ECs. Most importantly, we found that inhibition of importin-dependent NF-ĸB p65 nuclear translocation is a crucial part of the action of vioA leading to reduced NF-ĸB promotor activity and inflammatory gene expression. Knockdown experiments revealed a causal link between the cellular target NOP14 and the anti-inflammatory action of vioA, classifying the natural product as unique drug lead for anti-inflammatory therapeutics.Luisa D. BurgersBetty LuongYanfen LiMatthias P. FabritiusStylianos MichalakisChristoph A. ReichelRolf MüllerRobert FürstElsevierarticleVioprolide ANatural productEndothelial cellsInflammationProtein synthesisNucleolar protein 14Therapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112255- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Vioprolide A Natural product Endothelial cells Inflammation Protein synthesis Nucleolar protein 14 Therapeutics. Pharmacology RM1-950
spellingShingle	Vioprolide A Natural product Endothelial cells Inflammation Protein synthesis Nucleolar protein 14 Therapeutics. Pharmacology RM1-950 Luisa D. Burgers Betty Luong Yanfen Li Matthias P. Fabritius Stylianos Michalakis Christoph A. Reichel Rolf Müller Robert Fürst The natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation
description	Chronic inflammation is characterized by persisting leukocyte infiltration of the affected tissue, which is enabled by activated endothelial cells (ECs). Chronic inflammatory diseases remain a major pharmacotherapeutic challenge, and thus the search for novel drugs and drug targets is an ongoing demand. We have identified the natural product vioprolide A (vioA) to exert anti-inflammatory actions in vivo and in ECs in vitro through inhibition of its cellular target nucleolar protein 14 (NOP14). VioA attenuated the infiltration of microglia and macrophages during laser-induced murine choroidal neovascularization and the leukocyte trafficking through the vascular endothelium in the murine cremaster muscle. Mechanistic studies revealed that vioA downregulates EC adhesion molecules and the tumor necrosis factor receptor (TNFR) 1 by decreasing the de novo protein synthesis in ECs. Most importantly, we found that inhibition of importin-dependent NF-ĸB p65 nuclear translocation is a crucial part of the action of vioA leading to reduced NF-ĸB promotor activity and inflammatory gene expression. Knockdown experiments revealed a causal link between the cellular target NOP14 and the anti-inflammatory action of vioA, classifying the natural product as unique drug lead for anti-inflammatory therapeutics.
format	article
author	Luisa D. Burgers Betty Luong Yanfen Li Matthias P. Fabritius Stylianos Michalakis Christoph A. Reichel Rolf Müller Robert Fürst
author_facet	Luisa D. Burgers Betty Luong Yanfen Li Matthias P. Fabritius Stylianos Michalakis Christoph A. Reichel Rolf Müller Robert Fürst
author_sort	Luisa D. Burgers
title	The natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation
title_short	The natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation
title_full	The natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation
title_fullStr	The natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation
title_full_unstemmed	The natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation
title_sort	natural product vioprolide a exerts anti-inflammatory actions through inhibition of its cellular target nop14 and downregulation of importin-dependent nf-ĸb p65 nuclear translocation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/4d20bc27720141d9918bfdcaca1d4432
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The natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation

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