High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway

Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, wa...

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Autores principales:	Chien-Hsing Lee, Chi-Fu Chiang, Feng-Chih Kuo, Sheng-Chiang Su, Chia-Luen Huang, Jhih-Syuan Liu, Chieh-Hua Lu, Chang-Hsun Hsieh, Chih-Chien Wang, Chian-Her Lee, Pei-Hung Shen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	osteoarthritis hyaluronic acid GRP78 synoviocytes macrophage Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/219de49cc02a462ea56b93cf49b4387a
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spelling	oai:doaj.org-article:219de49cc02a462ea56b93cf49b4387a2021-11-11T17:20:03ZHigh-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway10.3390/ijms2221119171422-00671661-6596https://doaj.org/article/219de49cc02a462ea56b93cf49b4387a2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11917https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1β to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1β increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1β-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1β culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.Chien-Hsing LeeChi-Fu ChiangFeng-Chih KuoSheng-Chiang SuChia-Luen HuangJhih-Syuan LiuChieh-Hua LuChang-Hsun HsiehChih-Chien WangChian-Her LeePei-Hung ShenMDPI AGarticleosteoarthritishyaluronic acidGRP78synoviocytesmacrophageBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11917, p 11917 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	osteoarthritis hyaluronic acid GRP78 synoviocytes macrophage Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	osteoarthritis hyaluronic acid GRP78 synoviocytes macrophage Biology (General) QH301-705.5 Chemistry QD1-999 Chien-Hsing Lee Chi-Fu Chiang Feng-Chih Kuo Sheng-Chiang Su Chia-Luen Huang Jhih-Syuan Liu Chieh-Hua Lu Chang-Hsun Hsieh Chih-Chien Wang Chian-Her Lee Pei-Hung Shen High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway
description	Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1β to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1β increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1β-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1β culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.
format	article
author	Chien-Hsing Lee Chi-Fu Chiang Feng-Chih Kuo Sheng-Chiang Su Chia-Luen Huang Jhih-Syuan Liu Chieh-Hua Lu Chang-Hsun Hsieh Chih-Chien Wang Chian-Her Lee Pei-Hung Shen
author_facet	Chien-Hsing Lee Chi-Fu Chiang Feng-Chih Kuo Sheng-Chiang Su Chia-Luen Huang Jhih-Syuan Liu Chieh-Hua Lu Chang-Hsun Hsieh Chih-Chien Wang Chian-Her Lee Pei-Hung Shen
author_sort	Chien-Hsing Lee
title	High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway
title_short	High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway
title_full	High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway
title_fullStr	High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway
title_full_unstemmed	High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway
title_sort	high-molecular-weight hyaluronic acid inhibits il-1β-induced synovial inflammation and macrophage polarization through the grp78-nf-κb signaling pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/219de49cc02a462ea56b93cf49b4387a
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High-Molecular-Weight Hyaluronic Acid Inhibits IL-1β-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway

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