Cargando…

Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells

We aimed to investigate the impact of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammation in retinal glia. Inflammatory responses in mouse-derived glial cells and Wistar rat retinas were stimulated with administration of LPS. Cell survival and proinflammatory cytokine pro...

Descripción completa

Detalles Bibliográficos
Autores principales: Tawarayama, Hiroshi, Umeki, Kota, Inoue-Yanagimachi, Maki, Takahashi, Naoki, Hasegawa, Hirokazu, Himori, Noriko, Tsuda, Satoru, Kunikata, Hiroshi, Akaike, Takaaki, Nakazawa, Toru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352383/
https://www.ncbi.nlm.nih.gov/pubmed/37460786
http://dx.doi.org/10.1038/s41598-023-38696-4
_version_ 1785074503567540224
author Tawarayama, Hiroshi
Umeki, Kota
Inoue-Yanagimachi, Maki
Takahashi, Naoki
Hasegawa, Hirokazu
Himori, Noriko
Tsuda, Satoru
Kunikata, Hiroshi
Akaike, Takaaki
Nakazawa, Toru
author_facet Tawarayama, Hiroshi
Umeki, Kota
Inoue-Yanagimachi, Maki
Takahashi, Naoki
Hasegawa, Hirokazu
Himori, Noriko
Tsuda, Satoru
Kunikata, Hiroshi
Akaike, Takaaki
Nakazawa, Toru
author_sort Tawarayama, Hiroshi
collection PubMed
description We aimed to investigate the impact of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammation in retinal glia. Inflammatory responses in mouse-derived glial cells and Wistar rat retinas were stimulated with administration of LPS. Cell survival and proinflammatory cytokine production were examined using the Calcein-AM assay, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Retinal microglia were visualized with immunohistochemistry for Iba1. Administration of LPS (10 µg/mL) or GSSSG (less than 100 µM) did not affect survival of cultured primary Müller cells and established microglial cells (BV-2). RT-qPCR and ELISA indicated that GSSSG inhibited LPS-induced gene upregulation and protein secretion of proinflammatory cytokines in these glial cells and rat retinas. GSSSG inhibited LPS-induced activation of TGF-β-activated kinase 1 (TAK1), which is an upstream kinase of NF-κB, in BV-2 cells. Finally, in vivo experiments indicated that intravitreal administration of GSSSG but not its relative glutathione disulfide (GSSG) inhibited LPS (500 ng)-induced accumulation of Iba1-immunopositive microglia in rat retinas. Taken together, GSSSG has the potential to prevent pathogenesis of inflammation-associated ocular diseases by inhibiting proinflammatory cytokine expression in retinal glial cells.
format Online
Article
Text
id pubmed-10352383
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-103523832023-07-19 Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells Tawarayama, Hiroshi Umeki, Kota Inoue-Yanagimachi, Maki Takahashi, Naoki Hasegawa, Hirokazu Himori, Noriko Tsuda, Satoru Kunikata, Hiroshi Akaike, Takaaki Nakazawa, Toru Sci Rep Article We aimed to investigate the impact of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammation in retinal glia. Inflammatory responses in mouse-derived glial cells and Wistar rat retinas were stimulated with administration of LPS. Cell survival and proinflammatory cytokine production were examined using the Calcein-AM assay, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Retinal microglia were visualized with immunohistochemistry for Iba1. Administration of LPS (10 µg/mL) or GSSSG (less than 100 µM) did not affect survival of cultured primary Müller cells and established microglial cells (BV-2). RT-qPCR and ELISA indicated that GSSSG inhibited LPS-induced gene upregulation and protein secretion of proinflammatory cytokines in these glial cells and rat retinas. GSSSG inhibited LPS-induced activation of TGF-β-activated kinase 1 (TAK1), which is an upstream kinase of NF-κB, in BV-2 cells. Finally, in vivo experiments indicated that intravitreal administration of GSSSG but not its relative glutathione disulfide (GSSG) inhibited LPS (500 ng)-induced accumulation of Iba1-immunopositive microglia in rat retinas. Taken together, GSSSG has the potential to prevent pathogenesis of inflammation-associated ocular diseases by inhibiting proinflammatory cytokine expression in retinal glial cells. Nature Publishing Group UK 2023-07-17 /pmc/articles/PMC10352383/ /pubmed/37460786 http://dx.doi.org/10.1038/s41598-023-38696-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tawarayama, Hiroshi
Umeki, Kota
Inoue-Yanagimachi, Maki
Takahashi, Naoki
Hasegawa, Hirokazu
Himori, Noriko
Tsuda, Satoru
Kunikata, Hiroshi
Akaike, Takaaki
Nakazawa, Toru
Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells
title Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells
title_full Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells
title_fullStr Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells
title_full_unstemmed Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells
title_short Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells
title_sort glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352383/
https://www.ncbi.nlm.nih.gov/pubmed/37460786
http://dx.doi.org/10.1038/s41598-023-38696-4
work_keys_str_mv AT tawarayamahiroshi glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells
AT umekikota glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells
AT inoueyanagimachimaki glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells
AT takahashinaoki glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells
AT hasegawahirokazu glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells
AT himorinoriko glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells
AT tsudasatoru glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells
AT kunikatahiroshi glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells
AT akaiketakaaki glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells
AT nakazawatoru glutathionetrisulfidepreventslipopolysaccharideinducedretinalinflammationviainhibitionofproinflammatorycytokineproductioninglialcells