The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis

Abstract Endoplasmic reticulum (ER) stress is one of the hallmarks of neurodegenerative diseases. This study aimed to investigate the role of ER stress in interaction with inflammatory markers in patients with multiple sclerosis (MS). The participants in the current study were recruited in two age a...

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Main Authors: Zhila Maghbooli, Forough Azam Sayahpour, Tarlan Varzandi, Mahya Rouhollahi Masoumi, Mohammad Ali Sahraian
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-06996-6
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author Zhila Maghbooli
Forough Azam Sayahpour
Tarlan Varzandi
Mahya Rouhollahi Masoumi
Mohammad Ali Sahraian
author_facet Zhila Maghbooli
Forough Azam Sayahpour
Tarlan Varzandi
Mahya Rouhollahi Masoumi
Mohammad Ali Sahraian
author_sort Zhila Maghbooli
collection DOAJ
description Abstract Endoplasmic reticulum (ER) stress is one of the hallmarks of neurodegenerative diseases. This study aimed to investigate the role of ER stress in interaction with inflammatory markers in patients with multiple sclerosis (MS). The participants in the current study were recruited in two age and sex-matched groups: 44 recently diagnosed MS patients and 53 control subjects. Differential gene expression of C/EBP homologous protein (CHOP), 78-kDa glucose-regulated protein (GRP78), and circulating levels of interleukin (IL)-1β and tumor necrosis factor (TNF-α) were assessed in MS patients and controls. The results showed that serum levels of TNF-α were significantly higher in MS patients than in the control group (p = 0.01), but not IL-1β serum levels. As for ER stress markers, there were no changes in CHOP expression levels in MS patients compared to the control group (p = 0.2). In contrast, GRP78 showed significant upregulation in MS patients compared to the control group (p = 0.0001). This study showed that the interaction between GRP78 and TNF-α influences the risk of MS (beta = 1.43, 95%CI:1.09–1.87, p = 0.01). Our data suggest that the interaction between TNF-α and GRP78 may modulate ER stress in MS patients.
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spelling doaj-art-597f2a112cd84e18af010f42f2498a3f2025-08-20T04:01:24ZengNature PortfolioScientific Reports2045-23222025-07-011511810.1038/s41598-025-06996-6The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosisZhila Maghbooli0Forough Azam Sayahpour1Tarlan Varzandi2Mahya Rouhollahi Masoumi3Mohammad Ali Sahraian4Multiple Sclerosis Research Center, Neurosciences Institute, Tehran University of Medical SciencesDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECRMultiple Sclerosis Research Center, Neurosciences Institute, Tehran University of Medical SciencesDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECRMultiple Sclerosis Research Center, Neurosciences Institute, Tehran University of Medical SciencesAbstract Endoplasmic reticulum (ER) stress is one of the hallmarks of neurodegenerative diseases. This study aimed to investigate the role of ER stress in interaction with inflammatory markers in patients with multiple sclerosis (MS). The participants in the current study were recruited in two age and sex-matched groups: 44 recently diagnosed MS patients and 53 control subjects. Differential gene expression of C/EBP homologous protein (CHOP), 78-kDa glucose-regulated protein (GRP78), and circulating levels of interleukin (IL)-1β and tumor necrosis factor (TNF-α) were assessed in MS patients and controls. The results showed that serum levels of TNF-α were significantly higher in MS patients than in the control group (p = 0.01), but not IL-1β serum levels. As for ER stress markers, there were no changes in CHOP expression levels in MS patients compared to the control group (p = 0.2). In contrast, GRP78 showed significant upregulation in MS patients compared to the control group (p = 0.0001). This study showed that the interaction between GRP78 and TNF-α influences the risk of MS (beta = 1.43, 95%CI:1.09–1.87, p = 0.01). Our data suggest that the interaction between TNF-α and GRP78 may modulate ER stress in MS patients.https://doi.org/10.1038/s41598-025-06996-6Multiple sclerosisEndoplasmic reticulumGRP78TNF-α
spellingShingle Zhila Maghbooli
Forough Azam Sayahpour
Tarlan Varzandi
Mahya Rouhollahi Masoumi
Mohammad Ali Sahraian
The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis
Scientific Reports
Multiple sclerosis
Endoplasmic reticulum
GRP78
TNF-α
title The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis
title_full The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis
title_fullStr The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis
title_full_unstemmed The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis
title_short The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis
title_sort interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis
topic Multiple sclerosis
Endoplasmic reticulum
GRP78
TNF-α
url https://doi.org/10.1038/s41598-025-06996-6
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