Inhibitior of Bcl6 by FX1 protects DSS induced colitis mice through anti-inflammatory effects
IntroductionInflammatory bowel disease (IBD) is a complex immune-mediated condition, and biologics are the most commonly used drugs for its treatment. However, there are still cases of ineffective treatment. B-cell lymphoma 6 (Bcl6), a transcriptional suppressor, is known to have regulatory effects...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1558845/full |
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| author | Ruixian Liu Zhe Zhang Chuan Zhou Binbin Wang Muhan Zhang Yaxing Sun Yao Yao Yanru Zhang Yijia He Junzhi Yu Yimeng Xia Yan Liu Shiyang Ning Baisui Feng |
| author_facet | Ruixian Liu Zhe Zhang Chuan Zhou Binbin Wang Muhan Zhang Yaxing Sun Yao Yao Yanru Zhang Yijia He Junzhi Yu Yimeng Xia Yan Liu Shiyang Ning Baisui Feng |
| author_sort | Ruixian Liu |
| collection | DOAJ |
| description | IntroductionInflammatory bowel disease (IBD) is a complex immune-mediated condition, and biologics are the most commonly used drugs for its treatment. However, there are still cases of ineffective treatment. B-cell lymphoma 6 (Bcl6), a transcriptional suppressor, is known to have regulatory effects on multiple immune-associated cell subsets. FX1, a novel specific BCL6 Bric-à-brac (BTB) inhibitor, has shown positive effects in many disease models, but its effects and mechanisms in IBD control remain unclear.MethodsWe observed colon length and DAI score of colitis mice after treatment. HE staining section was used to evaluate colonic injury, while the expression of colonic pro-inflammatory cytokines by RT-qPCR. And differences in immune cell subsets between the two groups was analyzed by flow cytometry. Additionally, IHC and RT-qPCR were employed to evaluate the expression of colonic tight junction proteins. Furthermore, RAW264.7 cells and co-cultured Caco2 cells were detected by ELISA and RT-qPCR.ResultsIn the treat group, colitis symptoms in mice were significantly improved, and there was a decrease in proportion of macrophages and protection of intestinal mucosal integrity-indicating anti-inflammatory effects of FX1. In cell experiments, we found that FX1 decreased secretion of pro-inflammatory factors by macrophages and increased expression of tight junction proteins in Caco2 cells after co-culture.DiscussionThe experimental findings demonstrate the inhibitory effect of FX1 on inflammation in murine colitis model as well as its potential mechanism. BCL6 is a potential target for treating IBD. |
| format | Article |
| id | doaj-art-06aaadbb3afd4d1b8587fbe9905ccb03 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-06aaadbb3afd4d1b8587fbe9905ccb032025-08-20T02:15:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15588451558845Inhibitior of Bcl6 by FX1 protects DSS induced colitis mice through anti-inflammatory effectsRuixian LiuZhe ZhangChuan ZhouBinbin WangMuhan ZhangYaxing SunYao YaoYanru ZhangYijia HeJunzhi YuYimeng XiaYan LiuShiyang NingBaisui FengIntroductionInflammatory bowel disease (IBD) is a complex immune-mediated condition, and biologics are the most commonly used drugs for its treatment. However, there are still cases of ineffective treatment. B-cell lymphoma 6 (Bcl6), a transcriptional suppressor, is known to have regulatory effects on multiple immune-associated cell subsets. FX1, a novel specific BCL6 Bric-à-brac (BTB) inhibitor, has shown positive effects in many disease models, but its effects and mechanisms in IBD control remain unclear.MethodsWe observed colon length and DAI score of colitis mice after treatment. HE staining section was used to evaluate colonic injury, while the expression of colonic pro-inflammatory cytokines by RT-qPCR. And differences in immune cell subsets between the two groups was analyzed by flow cytometry. Additionally, IHC and RT-qPCR were employed to evaluate the expression of colonic tight junction proteins. Furthermore, RAW264.7 cells and co-cultured Caco2 cells were detected by ELISA and RT-qPCR.ResultsIn the treat group, colitis symptoms in mice were significantly improved, and there was a decrease in proportion of macrophages and protection of intestinal mucosal integrity-indicating anti-inflammatory effects of FX1. In cell experiments, we found that FX1 decreased secretion of pro-inflammatory factors by macrophages and increased expression of tight junction proteins in Caco2 cells after co-culture.DiscussionThe experimental findings demonstrate the inhibitory effect of FX1 on inflammation in murine colitis model as well as its potential mechanism. BCL6 is a potential target for treating IBD.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1558845/fullBCL6IBDpro-inflammatory cytokinesmacrophagetight junction proteins (TJPs) |
| spellingShingle | Ruixian Liu Zhe Zhang Chuan Zhou Binbin Wang Muhan Zhang Yaxing Sun Yao Yao Yanru Zhang Yijia He Junzhi Yu Yimeng Xia Yan Liu Shiyang Ning Baisui Feng Inhibitior of Bcl6 by FX1 protects DSS induced colitis mice through anti-inflammatory effects Frontiers in Immunology BCL6 IBD pro-inflammatory cytokines macrophage tight junction proteins (TJPs) |
| title | Inhibitior of Bcl6 by FX1 protects DSS induced colitis mice through anti-inflammatory effects |
| title_full | Inhibitior of Bcl6 by FX1 protects DSS induced colitis mice through anti-inflammatory effects |
| title_fullStr | Inhibitior of Bcl6 by FX1 protects DSS induced colitis mice through anti-inflammatory effects |
| title_full_unstemmed | Inhibitior of Bcl6 by FX1 protects DSS induced colitis mice through anti-inflammatory effects |
| title_short | Inhibitior of Bcl6 by FX1 protects DSS induced colitis mice through anti-inflammatory effects |
| title_sort | inhibitior of bcl6 by fx1 protects dss induced colitis mice through anti inflammatory effects |
| topic | BCL6 IBD pro-inflammatory cytokines macrophage tight junction proteins (TJPs) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1558845/full |
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