Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid Arthritis Synovial Fibroblasts

Mark J. Pearson; Magdalena A. Bik; Caroline Ospelt; Amy J. Naylor; Corinna Wehmeyer; Simon W. Jones; Christopher D. Buckley; Steffen Gay; Andrew Filer; Janet M. Lord

doi:10.1038/s41598-018-31173-3

Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid Arthritis Synovial Fibroblasts

Mark J. Pearson, Magdalena A. Bik, Caroline Ospelt, Amy J. Naylor, Corinna Wehmeyer, Simon W. Jones, Christopher D. Buckley, Steffen Gay, Andrew Filer, Janet M. Lord

Aston Medical School

Research output: Contribution to journal › Article › peer-review

Abstract

Galectin-9 (Gal9) has been postulated to have anti-infammatory properties based on the ability of
exogenous Gal9 to induce apoptosis in synovial fbroblasts in animal models of rheumatoid arthritis
(RA). Here we aimed to assess the potential role of endogenous Galectins, including Gal9, in the
infammatory pathology of the RA synovium in humans. Firstly expression of Galectins 1–9 was
determined in synovial fbroblasts (RASF) and dermal fbroblasts (DF) isolated from RA patients, the
latter representing a non-infamed site. We then further challenged the cells with pro-infammatory
TLR agonists and cytokines and assessed Galectin expression. Gal9 was found to be diferentially and
abundantly expressed in RASF compared to DF. Agonists of TLR3 and TLR4, along with IFNgamma were
also found to induce Gal9 expression in RASF. siRNA was then used to knock-down Gal9 expression
in RASF and the efects of this on apoptosis and cell viability were assessed. Increased apoptosis was
observed in RASF following Gal9 knock-down. We conclude that, unlike exogenous Gal9, endogenous
Gal9 is protective against apoptosis and enhances synovial fbroblast viability suggesting that its role in
RA is both pathogenic and pro-infammatory.

Original language	English
Article number	12887
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-31173-3
Publication status	Published - 27 Aug 2018

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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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@article{e3315eee3b2a4a8f9eac045d1926e03f,

title = "Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid Arthritis Synovial Fibroblasts",

abstract = "Galectin-9 (Gal9) has been postulated to have anti-infammatory properties based on the ability ofexogenous Gal9 to induce apoptosis in synovial fbroblasts in animal models of rheumatoid arthritis(RA). Here we aimed to assess the potential role of endogenous Galectins, including Gal9, in theinfammatory pathology of the RA synovium in humans. Firstly expression of Galectins 1–9 wasdetermined in synovial fbroblasts (RASF) and dermal fbroblasts (DF) isolated from RA patients, thelatter representing a non-infamed site. We then further challenged the cells with pro-infammatoryTLR agonists and cytokines and assessed Galectin expression. Gal9 was found to be diferentially andabundantly expressed in RASF compared to DF. Agonists of TLR3 and TLR4, along with IFNgamma werealso found to induce Gal9 expression in RASF. siRNA was then used to knock-down Gal9 expressionin RASF and the efects of this on apoptosis and cell viability were assessed. Increased apoptosis wasobserved in RASF following Gal9 knock-down. We conclude that, unlike exogenous Gal9, endogenousGal9 is protective against apoptosis and enhances synovial fbroblast viability suggesting that its role inRA is both pathogenic and pro-infammatory.",

author = "Pearson, {Mark J.} and Bik, {Magdalena A.} and Caroline Ospelt and Naylor, {Amy J.} and Corinna Wehmeyer and Jones, {Simon W.} and Buckley, {Christopher D.} and Steffen Gay and Andrew Filer and Lord, {Janet M.}",

note = "This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.",

year = "2018",

month = aug,

day = "27",

doi = "10.1038/s41598-018-31173-3",

language = "English",

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AU - Pearson, Mark J.

AU - Bik, Magdalena A.

AU - Ospelt, Caroline

AU - Naylor, Amy J.

AU - Wehmeyer, Corinna

AU - Jones, Simon W.

AU - Buckley, Christopher D.

AU - Gay, Steffen

AU - Filer, Andrew

AU - Lord, Janet M.

N1 - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PY - 2018/8/27

Y1 - 2018/8/27

N2 - Galectin-9 (Gal9) has been postulated to have anti-infammatory properties based on the ability ofexogenous Gal9 to induce apoptosis in synovial fbroblasts in animal models of rheumatoid arthritis(RA). Here we aimed to assess the potential role of endogenous Galectins, including Gal9, in theinfammatory pathology of the RA synovium in humans. Firstly expression of Galectins 1–9 wasdetermined in synovial fbroblasts (RASF) and dermal fbroblasts (DF) isolated from RA patients, thelatter representing a non-infamed site. We then further challenged the cells with pro-infammatoryTLR agonists and cytokines and assessed Galectin expression. Gal9 was found to be diferentially andabundantly expressed in RASF compared to DF. Agonists of TLR3 and TLR4, along with IFNgamma werealso found to induce Gal9 expression in RASF. siRNA was then used to knock-down Gal9 expressionin RASF and the efects of this on apoptosis and cell viability were assessed. Increased apoptosis wasobserved in RASF following Gal9 knock-down. We conclude that, unlike exogenous Gal9, endogenousGal9 is protective against apoptosis and enhances synovial fbroblast viability suggesting that its role inRA is both pathogenic and pro-infammatory.

AB - Galectin-9 (Gal9) has been postulated to have anti-infammatory properties based on the ability ofexogenous Gal9 to induce apoptosis in synovial fbroblasts in animal models of rheumatoid arthritis(RA). Here we aimed to assess the potential role of endogenous Galectins, including Gal9, in theinfammatory pathology of the RA synovium in humans. Firstly expression of Galectins 1–9 wasdetermined in synovial fbroblasts (RASF) and dermal fbroblasts (DF) isolated from RA patients, thelatter representing a non-infamed site. We then further challenged the cells with pro-infammatoryTLR agonists and cytokines and assessed Galectin expression. Gal9 was found to be diferentially andabundantly expressed in RASF compared to DF. Agonists of TLR3 and TLR4, along with IFNgamma werealso found to induce Gal9 expression in RASF. siRNA was then used to knock-down Gal9 expressionin RASF and the efects of this on apoptosis and cell viability were assessed. Increased apoptosis wasobserved in RASF following Gal9 knock-down. We conclude that, unlike exogenous Gal9, endogenousGal9 is protective against apoptosis and enhances synovial fbroblast viability suggesting that its role inRA is both pathogenic and pro-infammatory.

UR - http://www.nature.com/articles/s41598-018-31173-3

U2 - 10.1038/s41598-018-31173-3

DO - 10.1038/s41598-018-31173-3

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SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 12887

ER -

Endogenous Galectin-9 Suppresses Apoptosis in Human Rheumatoid Arthritis Synovial Fibroblasts

Abstract

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