Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats
Exogenous ganglioside GM1 has been reported to exert an immunomodulatory effect. We investigated the anti-inflammatory effect of GM1 ganglioside on endotoxin-induced uveitis (EIU) in rats and RAW 264.7 macrophages. Methods: EIU was induced in Lewis rats by administering a subcutaneous injection of l...
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MDPI AG
2022-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/5/727 |
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| author | Tzu-Heng Weng Chang-Chih Ke Yuahn-Sieh Huang |
| author_facet | Tzu-Heng Weng Chang-Chih Ke Yuahn-Sieh Huang |
| author_sort | Tzu-Heng Weng |
| collection | DOAJ |
| description | Exogenous ganglioside GM1 has been reported to exert an immunomodulatory effect. We investigated the anti-inflammatory effect of GM1 ganglioside on endotoxin-induced uveitis (EIU) in rats and RAW 264.7 macrophages. Methods: EIU was induced in Lewis rats by administering a subcutaneous injection of lipopolysaccharide (LPS). GM1 was injected intraperitoneally for three consecutive days prior to the LPS injection. Twenty-four hours after the LPS injection, the integrity of the blood-aqueous barrier was evaluated by determining the protein concentration and number of infiltrating cells in the aqueous humor (AqH). Immunohistochemical and Western blot analyses of the iris-ciliary body (ICB) were performed to evaluate the effect of GM1 on the LPS-induced expression of cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1). The effect of GM1 on proinflammatory mediators and signaling cascades was examined in LPS-stimulated RAW 264.7 cells using Western blotting and immunofluorescence staining to further clarify the underlying anti-inflammatory mechanism. Results: GM1 significantly reduced the protein concentration and number of infiltrating cells in the AqH of rats with EIU. GM1 also decreased the LPS-induced expression of the ICAM-1 and COX-2 proteins in the ICB. In RAW 264.7 cells, GM1 inhibited the proinflammatory mediators induced by LPS, including inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and this inhibitory effect was potentially mediated by suppressing reactive oxygen species (ROS)-mediated activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Conclusions: Based on this study, GM1 may be a potential anti-inflammatory agent for ocular inflammatory diseases. |
| first_indexed | 2024-03-10T03:15:58Z |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T03:15:58Z |
| publishDate | 2022-05-01 |
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| series | Biomolecules |
| spelling | doaj.art-d2bff8f35f8a4e8f98a486147e1f354d2023-11-23T10:14:42ZengMDPI AGBiomolecules2218-273X2022-05-0112572710.3390/biom12050727Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in RatsTzu-Heng Weng0Chang-Chih Ke1Yuahn-Sieh Huang2Department of Ophthalmology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Ophthalmology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 11490, TaiwanExogenous ganglioside GM1 has been reported to exert an immunomodulatory effect. We investigated the anti-inflammatory effect of GM1 ganglioside on endotoxin-induced uveitis (EIU) in rats and RAW 264.7 macrophages. Methods: EIU was induced in Lewis rats by administering a subcutaneous injection of lipopolysaccharide (LPS). GM1 was injected intraperitoneally for three consecutive days prior to the LPS injection. Twenty-four hours after the LPS injection, the integrity of the blood-aqueous barrier was evaluated by determining the protein concentration and number of infiltrating cells in the aqueous humor (AqH). Immunohistochemical and Western blot analyses of the iris-ciliary body (ICB) were performed to evaluate the effect of GM1 on the LPS-induced expression of cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1). The effect of GM1 on proinflammatory mediators and signaling cascades was examined in LPS-stimulated RAW 264.7 cells using Western blotting and immunofluorescence staining to further clarify the underlying anti-inflammatory mechanism. Results: GM1 significantly reduced the protein concentration and number of infiltrating cells in the AqH of rats with EIU. GM1 also decreased the LPS-induced expression of the ICAM-1 and COX-2 proteins in the ICB. In RAW 264.7 cells, GM1 inhibited the proinflammatory mediators induced by LPS, including inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and this inhibitory effect was potentially mediated by suppressing reactive oxygen species (ROS)-mediated activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Conclusions: Based on this study, GM1 may be a potential anti-inflammatory agent for ocular inflammatory diseases.https://www.mdpi.com/2218-273X/12/5/727GM1 gangliosideendotoxin-induced uveitisiris-ciliary bodyanti-inflammationRAW 264.7 cells |
| spellingShingle | Tzu-Heng Weng Chang-Chih Ke Yuahn-Sieh Huang Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats Biomolecules GM1 ganglioside endotoxin-induced uveitis iris-ciliary body anti-inflammation RAW 264.7 cells |
| title | Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats |
| title_full | Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats |
| title_fullStr | Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats |
| title_full_unstemmed | Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats |
| title_short | Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats |
| title_sort | anti inflammatory effects of gm1 ganglioside on endotoxin induced uveitis in rats |
| topic | GM1 ganglioside endotoxin-induced uveitis iris-ciliary body anti-inflammation RAW 264.7 cells |
| url | https://www.mdpi.com/2218-273X/12/5/727 |
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