Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice

Abstract Paraoxonase 1(PON1) is an HDL-associated protein, which metabolizes inflammatory, oxidized lipids associated with atherosclerotic plaque development. Because oxidized lipid mediators have also been implicated in the pathogenesis of rheumatoid arthritis (RA), we evaluated the role of PON1 in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Christina Charles-Schoeman, Jennifer Wang, Ani Shahbazian, Yuen Yin Lee, Xiaoyan Wang, Victor Grijalva, Ernest Brahn, Diana M. Shih, Asokan Devarajan, Christy Montano, Aldons J. Lusis, Srinivasa T. Reddy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa217fa44fbc4ec7b7007c4a1c01c859
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:aa217fa44fbc4ec7b7007c4a1c01c859
record_format	dspace
spelling	oai:doaj.org-article:aa217fa44fbc4ec7b7007c4a1c01c8592021-12-02T18:37:07ZSuppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice10.1038/s41598-020-74016-w2045-2322https://doaj.org/article/aa217fa44fbc4ec7b7007c4a1c01c8592020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-74016-whttps://doaj.org/toc/2045-2322Abstract Paraoxonase 1(PON1) is an HDL-associated protein, which metabolizes inflammatory, oxidized lipids associated with atherosclerotic plaque development. Because oxidized lipid mediators have also been implicated in the pathogenesis of rheumatoid arthritis (RA), we evaluated the role of PON1 in murine inflammatory arthritis. K/BxN serum transfer (STIA) or collagen antibody transfer (CAIA) was used for arthritis induction in B6 mice homozygous for the PON1 human transgene [PON1Tg], PON1 knock-out mice [PON1KO], and wild type littermate control mice [WT]. Experiments were also performed in K/BxN mice with chronic arthritis, and in RA patients and healthy controls. Arthritis activity in K/BxN mice was associated with a marked dyslipidemia, lower PON1 activity and higher bioactive lipid mediators (BLM), as well as a dysregulated hepatic lipid gene expression profile. Higher serum PON1 activity correlated with lower BLM and lower arthritis activity in both K/BxN mice and RA patients. Overexpression of the human PON1 transgene was associated with reduced inflammatory arthritis, which correlated strongly with higher circulating PON1 activity, upregulation of the hepatic glutathione pathway, and reduction of circulating BLM. These results implicate PON1 as a potential novel therapeutic target for joint disease in RA with potential for vascular benefit, which warrants further investigation.Christina Charles-SchoemanJennifer WangAni ShahbazianYuen Yin LeeXiaoyan WangVictor GrijalvaErnest BrahnDiana M. ShihAsokan DevarajanChristy MontanoAldons J. LusisSrinivasa T. ReddyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christina Charles-Schoeman Jennifer Wang Ani Shahbazian Yuen Yin Lee Xiaoyan Wang Victor Grijalva Ernest Brahn Diana M. Shih Asokan Devarajan Christy Montano Aldons J. Lusis Srinivasa T. Reddy Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice
description	Abstract Paraoxonase 1(PON1) is an HDL-associated protein, which metabolizes inflammatory, oxidized lipids associated with atherosclerotic plaque development. Because oxidized lipid mediators have also been implicated in the pathogenesis of rheumatoid arthritis (RA), we evaluated the role of PON1 in murine inflammatory arthritis. K/BxN serum transfer (STIA) or collagen antibody transfer (CAIA) was used for arthritis induction in B6 mice homozygous for the PON1 human transgene [PON1Tg], PON1 knock-out mice [PON1KO], and wild type littermate control mice [WT]. Experiments were also performed in K/BxN mice with chronic arthritis, and in RA patients and healthy controls. Arthritis activity in K/BxN mice was associated with a marked dyslipidemia, lower PON1 activity and higher bioactive lipid mediators (BLM), as well as a dysregulated hepatic lipid gene expression profile. Higher serum PON1 activity correlated with lower BLM and lower arthritis activity in both K/BxN mice and RA patients. Overexpression of the human PON1 transgene was associated with reduced inflammatory arthritis, which correlated strongly with higher circulating PON1 activity, upregulation of the hepatic glutathione pathway, and reduction of circulating BLM. These results implicate PON1 as a potential novel therapeutic target for joint disease in RA with potential for vascular benefit, which warrants further investigation.
format	article
author	Christina Charles-Schoeman Jennifer Wang Ani Shahbazian Yuen Yin Lee Xiaoyan Wang Victor Grijalva Ernest Brahn Diana M. Shih Asokan Devarajan Christy Montano Aldons J. Lusis Srinivasa T. Reddy
author_facet	Christina Charles-Schoeman Jennifer Wang Ani Shahbazian Yuen Yin Lee Xiaoyan Wang Victor Grijalva Ernest Brahn Diana M. Shih Asokan Devarajan Christy Montano Aldons J. Lusis Srinivasa T. Reddy
author_sort	Christina Charles-Schoeman
title	Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice
title_short	Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice
title_full	Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice
title_fullStr	Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice
title_full_unstemmed	Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice
title_sort	suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/aa217fa44fbc4ec7b7007c4a1c01c859
work_keys_str_mv	AT christinacharlesschoeman suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT jenniferwang suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT anishahbazian suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT yuenyinlee suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT xiaoyanwang suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT victorgrijalva suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT ernestbrahn suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT dianamshih suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT asokandevarajan suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT christymontano suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT aldonsjlusis suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice AT srinivasatreddy suppressionofinflammatoryarthritisinhumanserumparaoxonase1transgenicmice
_version_	1718377819080228864

Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice

Ejemplares similares