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Anti-dsDNA antibodies induce inflammation via endoplasmic reticulum stress in human mesangial cells
BACKGROUND: Anti-dsDNA antibodies play an important role in the pathogenesis of lupus nephritis (LN). Endoplasmic reticulum (ER) stress is a physical reaction under stressful condition and can cause inflammation when stimulation is sustained. This study investigated the roles of ER stress in anti-ds...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467615/ https://www.ncbi.nlm.nih.gov/pubmed/26040555 http://dx.doi.org/10.1186/s12967-015-0536-7 |
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author | Zhang, Hui Zhao, Chunmei Wang, Shuang Huang, Yuefang Wang, Hongyue Zhao, Jijun Yang, Niansheng |
author_facet | Zhang, Hui Zhao, Chunmei Wang, Shuang Huang, Yuefang Wang, Hongyue Zhao, Jijun Yang, Niansheng |
author_sort | Zhang, Hui |
collection | PubMed |
description | BACKGROUND: Anti-dsDNA antibodies play an important role in the pathogenesis of lupus nephritis (LN). Endoplasmic reticulum (ER) stress is a physical reaction under stressful condition and can cause inflammation when stimulation is sustained. This study investigated the roles of ER stress in anti-dsDNA antibody-induced inflammation response in human mesangial cells (HMCs). METHOD: Anti-dsDNA antibodies isolated from LN patients were used to stimulate HMCs. The expression of GRP78, PERK, p-PERK, p-eIF2α, ATF4, p-IRE1α, ATF6 and CHOP in HMCs was measured by western blot. NF-κB activation was detected by examining nuclear translocation of NF-κB p65. The expression and production of IL-1β, TNF-α and MCP-1 were examined by qPCR and ELISA. RESULTS: Flow cytometry and cellular ELISA showed that anti-dsDNA antibodies can bind to HMCs. The binding was not inhibited by blockage of Fc receptor. Anti-dsDNA antibody stimulation significantly enhanced the expression of GRP78, p-PERK, p-eIF2α and ATF4 in HMCs. However, no significant increase in the expression of p-IRE1α and ATF6 was found. In addition, anti-dsDNA antibodies also significantly increased the activation of NF-κB and upregulated the expression of IL-1β, TNF-α and MCP-1, which were suppressed by pretreatment of HMCs with chemical ER stress inhibitor 4-PBA. Transfection of specific ATF4 siRNA also significantly reduced the activation of NF-κB and expression of proinflammatory cytokines. CONCLUSION: Anti-dsDNA antibodies induce NF-κB activation and inflammation in HMCs via PERK-eIF2α-ATF4 ER stress pathway. |
format | Online Article Text |
id | pubmed-4467615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44676152015-06-16 Anti-dsDNA antibodies induce inflammation via endoplasmic reticulum stress in human mesangial cells Zhang, Hui Zhao, Chunmei Wang, Shuang Huang, Yuefang Wang, Hongyue Zhao, Jijun Yang, Niansheng J Transl Med Research BACKGROUND: Anti-dsDNA antibodies play an important role in the pathogenesis of lupus nephritis (LN). Endoplasmic reticulum (ER) stress is a physical reaction under stressful condition and can cause inflammation when stimulation is sustained. This study investigated the roles of ER stress in anti-dsDNA antibody-induced inflammation response in human mesangial cells (HMCs). METHOD: Anti-dsDNA antibodies isolated from LN patients were used to stimulate HMCs. The expression of GRP78, PERK, p-PERK, p-eIF2α, ATF4, p-IRE1α, ATF6 and CHOP in HMCs was measured by western blot. NF-κB activation was detected by examining nuclear translocation of NF-κB p65. The expression and production of IL-1β, TNF-α and MCP-1 were examined by qPCR and ELISA. RESULTS: Flow cytometry and cellular ELISA showed that anti-dsDNA antibodies can bind to HMCs. The binding was not inhibited by blockage of Fc receptor. Anti-dsDNA antibody stimulation significantly enhanced the expression of GRP78, p-PERK, p-eIF2α and ATF4 in HMCs. However, no significant increase in the expression of p-IRE1α and ATF6 was found. In addition, anti-dsDNA antibodies also significantly increased the activation of NF-κB and upregulated the expression of IL-1β, TNF-α and MCP-1, which were suppressed by pretreatment of HMCs with chemical ER stress inhibitor 4-PBA. Transfection of specific ATF4 siRNA also significantly reduced the activation of NF-κB and expression of proinflammatory cytokines. CONCLUSION: Anti-dsDNA antibodies induce NF-κB activation and inflammation in HMCs via PERK-eIF2α-ATF4 ER stress pathway. BioMed Central 2015-06-04 /pmc/articles/PMC4467615/ /pubmed/26040555 http://dx.doi.org/10.1186/s12967-015-0536-7 Text en © Zhang et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zhang, Hui Zhao, Chunmei Wang, Shuang Huang, Yuefang Wang, Hongyue Zhao, Jijun Yang, Niansheng Anti-dsDNA antibodies induce inflammation via endoplasmic reticulum stress in human mesangial cells |
title | Anti-dsDNA antibodies induce inflammation via endoplasmic reticulum stress in human mesangial cells |
title_full | Anti-dsDNA antibodies induce inflammation via endoplasmic reticulum stress in human mesangial cells |
title_fullStr | Anti-dsDNA antibodies induce inflammation via endoplasmic reticulum stress in human mesangial cells |
title_full_unstemmed | Anti-dsDNA antibodies induce inflammation via endoplasmic reticulum stress in human mesangial cells |
title_short | Anti-dsDNA antibodies induce inflammation via endoplasmic reticulum stress in human mesangial cells |
title_sort | anti-dsdna antibodies induce inflammation via endoplasmic reticulum stress in human mesangial cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467615/ https://www.ncbi.nlm.nih.gov/pubmed/26040555 http://dx.doi.org/10.1186/s12967-015-0536-7 |
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