MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralis
Abstract Trichinella spiralis (T. spiralis) has been reported to induce inflammation, which can cause immune system dysregulation. Myeloid differentiation primary response gene 88 (MyD88) is implicated in inflammation signalling pathways. TJ-M2010-5 is a novel MyD88 inhibitor with remarkable protect...
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BMC
2025-02-01
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| Series: | Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s13567-025-01459-2 |
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| author | Huifang Bai Qianqian Dang Guoliang Chen Lingfeng Xie Saining Wang Ning Jiang Xiaoxia Wu Shuyan Zhang Xuelin Wang |
| author_facet | Huifang Bai Qianqian Dang Guoliang Chen Lingfeng Xie Saining Wang Ning Jiang Xiaoxia Wu Shuyan Zhang Xuelin Wang |
| author_sort | Huifang Bai |
| collection | DOAJ |
| description | Abstract Trichinella spiralis (T. spiralis) has been reported to induce inflammation, which can cause immune system dysregulation. Myeloid differentiation primary response gene 88 (MyD88) is implicated in inflammation signalling pathways. TJ-M2010-5 is a novel MyD88 inhibitor with remarkable protective effects against several diseases. However, the precise mechanism of TJ-M2010-5’s involvement in spleen impairment and inflammation in the early infection of T. spiralis has yet to be fully elucidated. This study analysed histological, inflammation, and macrophage polarisation of the early T. spiralis-infected mice treated with TJ-M2010-5. MyD88 promoter methylation results showed that the methylation levels in the 5 d group were lower compared to the control group (P < 0.05). Furthermore, the methylation led to an imbalance in anti-inflammatory regulation in the infected mice. After TJ-M2010-5 treatment, spleen impairment was reduced. Sequencing analysis showed that TJ-M2010-5 significantly up-regulated 9 and down-regulated 10 miRNAs compared with the 5 d group. A dual-luciferase reporter assay further revealed that miR-136-5p is involved in the TJ-M2010-5 treatment by targeting AKT3. In RAW264.7 cells, TJ-M2010-5 pre-treatment significantly reversed the M1 polarisation and inhibited nitric oxide (NO) production. LC–MS/MS results showed TJ-M2010-5 was hepatosplenic-targeted. In conclusion, the study demonstrates that TJ-M2010-5 could effectively alleviate spleen impairment and reduce inflammation in mice infected with T. spiralis in its early stages by blocking the activation of PI3K/miR-136-5p/AKT3. |
| format | Article |
| id | doaj-art-8a28a2ea79b8456b84af7157fa2c9bb0 |
| institution | Kabale University |
| issn | 1297-9716 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj-art-8a28a2ea79b8456b84af7157fa2c9bb02025-02-09T12:50:08ZengBMCVeterinary Research1297-97162025-02-0156111610.1186/s13567-025-01459-2MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralisHuifang Bai0Qianqian Dang1Guoliang Chen2Lingfeng Xie3Saining Wang4Ning Jiang5Xiaoxia Wu6Shuyan Zhang7Xuelin Wang8State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin UniversityAbstract Trichinella spiralis (T. spiralis) has been reported to induce inflammation, which can cause immune system dysregulation. Myeloid differentiation primary response gene 88 (MyD88) is implicated in inflammation signalling pathways. TJ-M2010-5 is a novel MyD88 inhibitor with remarkable protective effects against several diseases. However, the precise mechanism of TJ-M2010-5’s involvement in spleen impairment and inflammation in the early infection of T. spiralis has yet to be fully elucidated. This study analysed histological, inflammation, and macrophage polarisation of the early T. spiralis-infected mice treated with TJ-M2010-5. MyD88 promoter methylation results showed that the methylation levels in the 5 d group were lower compared to the control group (P < 0.05). Furthermore, the methylation led to an imbalance in anti-inflammatory regulation in the infected mice. After TJ-M2010-5 treatment, spleen impairment was reduced. Sequencing analysis showed that TJ-M2010-5 significantly up-regulated 9 and down-regulated 10 miRNAs compared with the 5 d group. A dual-luciferase reporter assay further revealed that miR-136-5p is involved in the TJ-M2010-5 treatment by targeting AKT3. In RAW264.7 cells, TJ-M2010-5 pre-treatment significantly reversed the M1 polarisation and inhibited nitric oxide (NO) production. LC–MS/MS results showed TJ-M2010-5 was hepatosplenic-targeted. In conclusion, the study demonstrates that TJ-M2010-5 could effectively alleviate spleen impairment and reduce inflammation in mice infected with T. spiralis in its early stages by blocking the activation of PI3K/miR-136-5p/AKT3.https://doi.org/10.1186/s13567-025-01459-2TJ-M2010-5MyD88inflammationTrichinella spiralismethylation |
| spellingShingle | Huifang Bai Qianqian Dang Guoliang Chen Lingfeng Xie Saining Wang Ning Jiang Xiaoxia Wu Shuyan Zhang Xuelin Wang MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralis Veterinary Research TJ-M2010-5 MyD88 inflammation Trichinella spiralis methylation |
| title | MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralis |
| title_full | MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralis |
| title_fullStr | MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralis |
| title_full_unstemmed | MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralis |
| title_short | MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralis |
| title_sort | myd88 inhibitor tj m2010 5 alleviates spleen impairment and inflammation by inhibiting the pi3k mir 136 5p akt3 pathway in the early infection of trichinella spiralis |
| topic | TJ-M2010-5 MyD88 inflammation Trichinella spiralis methylation |
| url | https://doi.org/10.1186/s13567-025-01459-2 |
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