Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis
Ulcerative colitis (UC) is a chronic intestinal inflammatory disease with complex etiology. Interleukin-35 (IL-35), as a cytokine with immunomodulatory function, has been shown to have therapeutic effects on UC, but its mechanism is not yet clear. Therefore, we constructed Pichia pastoris stably exp...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2024/3282679 |
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| author | Baoren Zhang Chenglu Sun Yanglin Zhu Hong Qin Dejun Kong Jingyi Zhang Bo Shao Xiang Li Shaohua Ren Hongda Wang Jingpeng Hao Hao Wang |
| author_facet | Baoren Zhang Chenglu Sun Yanglin Zhu Hong Qin Dejun Kong Jingyi Zhang Bo Shao Xiang Li Shaohua Ren Hongda Wang Jingpeng Hao Hao Wang |
| author_sort | Baoren Zhang |
| collection | DOAJ |
| description | Ulcerative colitis (UC) is a chronic intestinal inflammatory disease with complex etiology. Interleukin-35 (IL-35), as a cytokine with immunomodulatory function, has been shown to have therapeutic effects on UC, but its mechanism is not yet clear. Therefore, we constructed Pichia pastoris stably expressing IL-35 which enables the cytokines to reach the diseased mucosa, and explored whether upregulation of T-cell protein tyrosine phosphatase (TCPTP) in macrophages is involved in the mechanisms of IL-35-mediated attenuation of UC. After the successful construction of engineered bacteria expressing IL-35, a colitis model was successfully induced by giving BALB/c mice a solution containing 3% dextran sulfate sodium (DSS). Mice were treated with Pichia/IL-35, empty plasmid-transformed Pichia (Pichia/0), or PBS by gavage, respectively. The expression of TCPTP in macrophages (RAW264.7, BMDMs) and intestinal tissues after IL-35 treatment was detected. After administration of Pichia/IL-35, the mice showed significant improvement in weight loss, bloody stools, and shortened colon. Colon pathology also showed that the inflammatory condition of mice in the Pichia/IL-35 treatment group was alleviated. Notably, Pichia/IL-35 treatment not only increases local M2 macrophages but also decreases the expression of inflammatory cytokine IL-6 in the colon. With Pichia/IL-35 treatment, the proportion of M1 macrophages, Th17, and Th1 cells in mouse MLNs were markedly decreased, while Tregs were significantly increased. In vitro experiments, IL-35 significantly promoted the expression of TCPTP in macrophages stimulated with LPS. Similarly, the mice in the Pichia/IL-35 group also expressed more TCPTP than that of the untreated group and the Pichia/0 group. |
| format | Article |
| id | doaj-art-dabd1b01da144a05b009cc2479fafab9 |
| institution | Kabale University |
| issn | 1466-1861 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-dabd1b01da144a05b009cc2479fafab92025-02-03T01:30:20ZengWileyMediators of Inflammation1466-18612024-01-01202410.1155/2024/3282679Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental ColitisBaoren Zhang0Chenglu Sun1Yanglin Zhu2Hong Qin3Dejun Kong4Jingyi Zhang5Bo Shao6Xiang Li7Shaohua Ren8Hongda Wang9Jingpeng Hao10Hao Wang11Department of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgerySchool of MedicineDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryUlcerative colitis (UC) is a chronic intestinal inflammatory disease with complex etiology. Interleukin-35 (IL-35), as a cytokine with immunomodulatory function, has been shown to have therapeutic effects on UC, but its mechanism is not yet clear. Therefore, we constructed Pichia pastoris stably expressing IL-35 which enables the cytokines to reach the diseased mucosa, and explored whether upregulation of T-cell protein tyrosine phosphatase (TCPTP) in macrophages is involved in the mechanisms of IL-35-mediated attenuation of UC. After the successful construction of engineered bacteria expressing IL-35, a colitis model was successfully induced by giving BALB/c mice a solution containing 3% dextran sulfate sodium (DSS). Mice were treated with Pichia/IL-35, empty plasmid-transformed Pichia (Pichia/0), or PBS by gavage, respectively. The expression of TCPTP in macrophages (RAW264.7, BMDMs) and intestinal tissues after IL-35 treatment was detected. After administration of Pichia/IL-35, the mice showed significant improvement in weight loss, bloody stools, and shortened colon. Colon pathology also showed that the inflammatory condition of mice in the Pichia/IL-35 treatment group was alleviated. Notably, Pichia/IL-35 treatment not only increases local M2 macrophages but also decreases the expression of inflammatory cytokine IL-6 in the colon. With Pichia/IL-35 treatment, the proportion of M1 macrophages, Th17, and Th1 cells in mouse MLNs were markedly decreased, while Tregs were significantly increased. In vitro experiments, IL-35 significantly promoted the expression of TCPTP in macrophages stimulated with LPS. Similarly, the mice in the Pichia/IL-35 group also expressed more TCPTP than that of the untreated group and the Pichia/0 group.http://dx.doi.org/10.1155/2024/3282679 |
| spellingShingle | Baoren Zhang Chenglu Sun Yanglin Zhu Hong Qin Dejun Kong Jingyi Zhang Bo Shao Xiang Li Shaohua Ren Hongda Wang Jingpeng Hao Hao Wang Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis Mediators of Inflammation |
| title | Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis |
| title_full | Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis |
| title_fullStr | Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis |
| title_full_unstemmed | Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis |
| title_short | Upregulation of TCPTP in Macrophages Is Involved in IL-35 Mediated Attenuation of Experimental Colitis |
| title_sort | upregulation of tcptp in macrophages is involved in il 35 mediated attenuation of experimental colitis |
| url | http://dx.doi.org/10.1155/2024/3282679 |
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