Endoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages

Abstract In many diseases, misfolded proteins accumulate within the endoplasmic reticulum (ER), leading to ER stress. In response, the cell initiates the unfolded protein response (UPR) to reestablish homeostasis. Additionally, in response to ER stress, various cell types mount an inflammatory respo...

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Autores principales:	Cristina L. Sanchez, Savannah G. Sims, John D. Nowery, Gordon P. Meares
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3f1160e39c86495c88208f8c2c5b0938
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spelling	oai:doaj.org-article:3f1160e39c86495c88208f8c2c5b09382021-12-02T15:10:02ZEndoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages10.1038/s41598-019-51481-62045-2322https://doaj.org/article/3f1160e39c86495c88208f8c2c5b09382019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51481-6https://doaj.org/toc/2045-2322Abstract In many diseases, misfolded proteins accumulate within the endoplasmic reticulum (ER), leading to ER stress. In response, the cell initiates the unfolded protein response (UPR) to reestablish homeostasis. Additionally, in response to ER stress, various cell types mount an inflammatory response involving interleukin (IL)-6. While IL-6 has been widely studied, the impact of ER stress on other members of the IL-6 cytokine family, including oncostatin (OSM), IL-11, ciliary neurotrophic factor (CNTF), and leukemia inhibitor factor (LIF) remains to be elucidated. Here, we have examined the expression of the IL-6 family cytokines in response to pharmacologically-induced ER stress in astrocytes and macrophages, which express IL-6 in response to ER stress through different mechanisms. Our findings indicate that, in astrocytes, ER stress regulates mRNA expression of the IL-6 family of cytokines that is, in part, mediated by PKR-like ER kinase (PERK) and Janus kinase (JAK) 1. Additionally, in astrocytes, CNTF expression was suppressed through a PERK-dependent mechanism. Macrophages display a different profile of expression of the IL-6 family that is largely independent of PERK. However, IL-6 expression in macrophages was dependent on JAK signaling. Overall, this study demonstrates the cell-specific and differential mechanisms controlling expression of the IL-6 family of cytokines in response to ER stress.Cristina L. SanchezSavannah G. SimsJohn D. NoweryGordon P. MearesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cristina L. Sanchez Savannah G. Sims John D. Nowery Gordon P. Meares Endoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages
description	Abstract In many diseases, misfolded proteins accumulate within the endoplasmic reticulum (ER), leading to ER stress. In response, the cell initiates the unfolded protein response (UPR) to reestablish homeostasis. Additionally, in response to ER stress, various cell types mount an inflammatory response involving interleukin (IL)-6. While IL-6 has been widely studied, the impact of ER stress on other members of the IL-6 cytokine family, including oncostatin (OSM), IL-11, ciliary neurotrophic factor (CNTF), and leukemia inhibitor factor (LIF) remains to be elucidated. Here, we have examined the expression of the IL-6 family cytokines in response to pharmacologically-induced ER stress in astrocytes and macrophages, which express IL-6 in response to ER stress through different mechanisms. Our findings indicate that, in astrocytes, ER stress regulates mRNA expression of the IL-6 family of cytokines that is, in part, mediated by PKR-like ER kinase (PERK) and Janus kinase (JAK) 1. Additionally, in astrocytes, CNTF expression was suppressed through a PERK-dependent mechanism. Macrophages display a different profile of expression of the IL-6 family that is largely independent of PERK. However, IL-6 expression in macrophages was dependent on JAK signaling. Overall, this study demonstrates the cell-specific and differential mechanisms controlling expression of the IL-6 family of cytokines in response to ER stress.
format	article
author	Cristina L. Sanchez Savannah G. Sims John D. Nowery Gordon P. Meares
author_facet	Cristina L. Sanchez Savannah G. Sims John D. Nowery Gordon P. Meares
author_sort	Cristina L. Sanchez
title	Endoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages
title_short	Endoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages
title_full	Endoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages
title_fullStr	Endoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages
title_full_unstemmed	Endoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages
title_sort	endoplasmic reticulum stress differentially modulates the il-6 family of cytokines in murine astrocytes and macrophages
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/3f1160e39c86495c88208f8c2c5b0938
work_keys_str_mv	AT cristinalsanchez endoplasmicreticulumstressdifferentiallymodulatestheil6familyofcytokinesinmurineastrocytesandmacrophages AT savannahgsims endoplasmicreticulumstressdifferentiallymodulatestheil6familyofcytokinesinmurineastrocytesandmacrophages AT johndnowery endoplasmicreticulumstressdifferentiallymodulatestheil6familyofcytokinesinmurineastrocytesandmacrophages AT gordonpmeares endoplasmicreticulumstressdifferentiallymodulatestheil6familyofcytokinesinmurineastrocytesandmacrophages
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Endoplasmic reticulum stress differentially modulates the IL-6 family of cytokines in murine astrocytes and macrophages

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