Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation
A growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9. Therefore, research into blocking TLR activation to treat these disorders has become a hot topic. Here, we report the im...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/6541729 |
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| author | Wancheng Liu Xuejiao Yang Ning Wang Shijun Fan Yuanfeng Zhu Xinchuan Zheng Yan Li |
| author_facet | Wancheng Liu Xuejiao Yang Ning Wang Shijun Fan Yuanfeng Zhu Xinchuan Zheng Yan Li |
| author_sort | Wancheng Liu |
| collection | DOAJ |
| description | A growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9. Therefore, research into blocking TLR activation to treat these disorders has become a hot topic. Here, we report the immunomodulatory properties of a nonstimulatory CpG-containing oligodeoxynucleotide (CpG-ODN), CpG-c41, which had previously only been known as a TLR9 antagonist. In this study, we found that both in vitro and in vivo CpG-c41 decreased levels of various proinflammatory factors that were induced by single activation or coactivation of intracellular TLRs, but not membrane-bound TLRs, no matter what downstream signal pathways the TLRs depend on. Moreover, CpG-c41 attenuated excessive inflammation in the imiquimod-induced psoriasis-like mouse model of skin inflammation by suppressing immune cell infiltration and release of inflammatory factors. We also found evidence that the immunosuppressive effects of CpG-c41 on other intracellular TLRs are mediated by a TLR9-independent mechanism. These results suggest that CpG-c41 acts as an upstream of signaling cascades, perhaps on the processes of ligand internalization and transfer. Taken together, these results suggest that CpG-c41 disrupts various aspects of intracellular TLR activation and provides a deeper insight into the regulation of innate immunity. |
| format | Article |
| id | doaj-art-8693eba6758c47b6a1a0b18a9f571c8a |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-8693eba6758c47b6a1a0b18a9f571c8a2025-02-03T01:09:45ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/65417296541729Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated InflammationWancheng Liu0Xuejiao Yang1Ning Wang2Shijun Fan3Yuanfeng Zhu4Xinchuan Zheng5Yan Li6Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, ChinaMedical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, ChinaMedical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, ChinaMedical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, ChinaMedical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, ChinaMedical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, ChinaMedical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, ChinaA growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9. Therefore, research into blocking TLR activation to treat these disorders has become a hot topic. Here, we report the immunomodulatory properties of a nonstimulatory CpG-containing oligodeoxynucleotide (CpG-ODN), CpG-c41, which had previously only been known as a TLR9 antagonist. In this study, we found that both in vitro and in vivo CpG-c41 decreased levels of various proinflammatory factors that were induced by single activation or coactivation of intracellular TLRs, but not membrane-bound TLRs, no matter what downstream signal pathways the TLRs depend on. Moreover, CpG-c41 attenuated excessive inflammation in the imiquimod-induced psoriasis-like mouse model of skin inflammation by suppressing immune cell infiltration and release of inflammatory factors. We also found evidence that the immunosuppressive effects of CpG-c41 on other intracellular TLRs are mediated by a TLR9-independent mechanism. These results suggest that CpG-c41 acts as an upstream of signaling cascades, perhaps on the processes of ligand internalization and transfer. Taken together, these results suggest that CpG-c41 disrupts various aspects of intracellular TLR activation and provides a deeper insight into the regulation of innate immunity.http://dx.doi.org/10.1155/2017/6541729 |
| spellingShingle | Wancheng Liu Xuejiao Yang Ning Wang Shijun Fan Yuanfeng Zhu Xinchuan Zheng Yan Li Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation Mediators of Inflammation |
| title | Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation |
| title_full | Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation |
| title_fullStr | Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation |
| title_full_unstemmed | Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation |
| title_short | Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation |
| title_sort | multiple immunosuppressive effects of cpg c41 on intracellular tlr mediated inflammation |
| url | http://dx.doi.org/10.1155/2017/6541729 |
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