Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice

Anti-rheumatoid arthritis (RA) effects of α-tocopherol (α-T) have been shown in human patients in a double-blind trial. However, the effects of α-T and its derivatives on fibroblast-like synoviocytes (FLS) during the pathogenesis of RA remain unclear. In the present study, we compared the expression...

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Main Authors: Susumu Hama, Naoko Kirimura, Aki Obara, Hirokatsu Takatsu, Kentaro Kogure
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/4/1425
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author Susumu Hama
Naoko Kirimura
Aki Obara
Hirokatsu Takatsu
Kentaro Kogure
author_facet Susumu Hama
Naoko Kirimura
Aki Obara
Hirokatsu Takatsu
Kentaro Kogure
author_sort Susumu Hama
collection DOAJ
description Anti-rheumatoid arthritis (RA) effects of α-tocopherol (α-T) have been shown in human patients in a double-blind trial. However, the effects of α-T and its derivatives on fibroblast-like synoviocytes (FLS) during the pathogenesis of RA remain unclear. In the present study, we compared the expression levels of genes related to RA progression in FLS treated with α-T, succinic ester of α-T (TS), and phosphate ester of α-T (TP), as determined via RT-PCR. The mRNA levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, and MMP-13 were reduced by treatment with TP without cytotoxicity, while α-T and TS did not show such effects. Furthermore, intraperitoneal injection of TP ameliorated the edema of the foot and joint and improved the arthritis score in laminarin-induced RA model mice. Therefore, TP exerted anti-RA effects through by inhibiting RA-related gene expression.
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spelling doaj.art-84775a1e8926413fbbb4351ff535757d2023-11-23T21:23:48ZengMDPI AGMolecules1420-30492022-02-01274142510.3390/molecules27041425Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in MiceSusumu Hama0Naoko Kirimura1Aki Obara2Hirokatsu Takatsu3Kentaro Kogure4Faculty of Pharmacy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo 202-8585, JapanDepartment of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, JapanDepartment of Analytical Chemistry, Kyorin University, Tokyo 181-8612, JapanDepartment of Analytical Chemistry, Kyorin University, Tokyo 181-8612, JapanGraduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8505, JapanAnti-rheumatoid arthritis (RA) effects of α-tocopherol (α-T) have been shown in human patients in a double-blind trial. However, the effects of α-T and its derivatives on fibroblast-like synoviocytes (FLS) during the pathogenesis of RA remain unclear. In the present study, we compared the expression levels of genes related to RA progression in FLS treated with α-T, succinic ester of α-T (TS), and phosphate ester of α-T (TP), as determined via RT-PCR. The mRNA levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, and MMP-13 were reduced by treatment with TP without cytotoxicity, while α-T and TS did not show such effects. Furthermore, intraperitoneal injection of TP ameliorated the edema of the foot and joint and improved the arthritis score in laminarin-induced RA model mice. Therefore, TP exerted anti-RA effects through by inhibiting RA-related gene expression.https://www.mdpi.com/1420-3049/27/4/1425α-tocopheroltocopheryl phosphatetocopheryl succinaterheumatoid arthritis
spellingShingle Susumu Hama
Naoko Kirimura
Aki Obara
Hirokatsu Takatsu
Kentaro Kogure
Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice
Molecules
α-tocopherol
tocopheryl phosphate
tocopheryl succinate
rheumatoid arthritis
title Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice
title_full Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice
title_fullStr Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice
title_full_unstemmed Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice
title_short Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice
title_sort tocopheryl phosphate inhibits rheumatoid arthritis related gene expression in vitro and ameliorates arthritic symptoms in mice
topic α-tocopherol
tocopheryl phosphate
tocopheryl succinate
rheumatoid arthritis
url https://www.mdpi.com/1420-3049/27/4/1425
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