Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells
Abstract 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 cyt...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38696-4 |
| _version_ | 1797774128369893376 |
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| author | Hiroshi Tawarayama Kota Umeki Maki Inoue-Yanagimachi Naoki Takahashi Hirokazu Hasegawa Noriko Himori Satoru Tsuda Hiroshi Kunikata Takaaki Akaike Toru Nakazawa |
| author_facet | Hiroshi Tawarayama Kota Umeki Maki Inoue-Yanagimachi Naoki Takahashi Hirokazu Hasegawa Noriko Himori Satoru Tsuda Hiroshi Kunikata Takaaki Akaike Toru Nakazawa |
| author_sort | Hiroshi Tawarayama |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T22:16:29Z |
| format | Article |
| id | doaj.art-05aac5d878cf48669ca0536413815423 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T22:16:29Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-05aac5d878cf48669ca05364138154232023-07-23T11:15:24ZengNature PortfolioScientific Reports2045-23222023-07-0113111010.1038/s41598-023-38696-4Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cellsHiroshi Tawarayama0Kota Umeki1Maki Inoue-Yanagimachi2Naoki Takahashi3Hirokazu Hasegawa4Noriko Himori5Satoru Tsuda6Hiroshi Kunikata7Takaaki Akaike8Toru Nakazawa9Department of Ophthalmology, Tohoku University Graduate School of MedicineDepartment of Ophthalmology, Tohoku University Graduate School of MedicineDepartment of Ophthalmology, Tohoku University Graduate School of MedicineDepartment of Ophthalmology, Tohoku University Graduate School of MedicineDepartment of Ophthalmology, Tohoku University Graduate School of MedicineDepartment of Ophthalmology, Tohoku University Graduate School of MedicineDepartment of Ophthalmology, Tohoku University Graduate School of MedicineDepartment of Ophthalmology, Tohoku University Graduate School of MedicineDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of MedicineDepartment of Ophthalmology, Tohoku University Graduate School of MedicineAbstract 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.https://doi.org/10.1038/s41598-023-38696-4 |
| spellingShingle | Hiroshi Tawarayama Kota Umeki Maki Inoue-Yanagimachi Naoki Takahashi Hirokazu Hasegawa Noriko Himori Satoru Tsuda Hiroshi Kunikata Takaaki Akaike Toru Nakazawa Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-023-38696-4 |
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