Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils
The loss of inhibitor of differentiation-2 (ID2) could lead to the development of colitis in mice, supplementation with exogenous ID2 protein might be a potential strategy to ameliorate colitis. In this study, the effects of ID2 protein supplementation on Dextran sodium sulfate (DSS)-induced colitis...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:fbab3ce285ee45ada945b4a9d7a958f92021-11-04T06:30:46ZInhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils1664-322410.3389/fimmu.2021.760999https://doaj.org/article/fbab3ce285ee45ada945b4a9d7a958f92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.760999/fullhttps://doaj.org/toc/1664-3224The loss of inhibitor of differentiation-2 (ID2) could lead to the development of colitis in mice, supplementation with exogenous ID2 protein might be a potential strategy to ameliorate colitis. In this study, the effects of ID2 protein supplementation on Dextran sodium sulfate (DSS)-induced colitis were investigated. Firstly, we confirmed that the expression of ID2 was reduced in the colon tissues of DSS-induced colitis mice and patients with ulcerative colitis (UC). Then, we constructed a recombinant plasmid containing the human Id2 gene and expressed it in Escherichia coli (E. coli) successfully. After purification and identification, purified hID2 could ameliorate DSS-induced colitis efficiently in mice by improving disease symptoms, decreasing the levels of proinflammatory cytokines in colon tissues, maintaining the integrity of intestinal barrier and reducing the infiltration of neutrophils and macrophages in the colon. Further study showed that hID2 could be endocytosed efficiently by neutrophils and macrophages, and hID2 lost its protection function against colitis when neutrophils were depleted with an anti-Gr-1 antibody. hID2 decreased the mRNA levels of IL-6, IL-1β and TNF-α in lipopolysaccharides (LPS)-stimulated neutrophils and efficiently inhibited the activation of NF-κB signalling pathway in neutrophils. Interestingly, hID2 showed a synergistic role in inhibition of NF-κB activation with pyrrolidine dithiocarbamic acid (PDTC), an inhibitor of NF-κB activation. Therefore, this study demonstrated the potential use of hID2 to treat UC, and hID2 protein might be a promising anti-inflammatory agent that targets the NF-κB signalling pathway in neutrophils.Jie RenDong YanYichun WangJiaojiao ZhangMin LiWancheng XiongXueqian JingPuze LiWeidong ZhaoXiwen XiongMinna WuGenshen ZhongFrontiers Media S.A.articleInhibitor of differentiation-2 (ID2)ulcerative colitis (UC)intestinal barrierneutrophilsnuclear factor kappa B (NF-κB)recombinant proteinImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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DOAJ |
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EN |
| topic |
Inhibitor of differentiation-2 (ID2) ulcerative colitis (UC) intestinal barrier neutrophils nuclear factor kappa B (NF-κB) recombinant protein Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
Inhibitor of differentiation-2 (ID2) ulcerative colitis (UC) intestinal barrier neutrophils nuclear factor kappa B (NF-κB) recombinant protein Immunologic diseases. Allergy RC581-607 Jie Ren Dong Yan Yichun Wang Jiaojiao Zhang Min Li Wancheng Xiong Xueqian Jing Puze Li Weidong Zhao Xiwen Xiong Minna Wu Genshen Zhong Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils |
| description |
The loss of inhibitor of differentiation-2 (ID2) could lead to the development of colitis in mice, supplementation with exogenous ID2 protein might be a potential strategy to ameliorate colitis. In this study, the effects of ID2 protein supplementation on Dextran sodium sulfate (DSS)-induced colitis were investigated. Firstly, we confirmed that the expression of ID2 was reduced in the colon tissues of DSS-induced colitis mice and patients with ulcerative colitis (UC). Then, we constructed a recombinant plasmid containing the human Id2 gene and expressed it in Escherichia coli (E. coli) successfully. After purification and identification, purified hID2 could ameliorate DSS-induced colitis efficiently in mice by improving disease symptoms, decreasing the levels of proinflammatory cytokines in colon tissues, maintaining the integrity of intestinal barrier and reducing the infiltration of neutrophils and macrophages in the colon. Further study showed that hID2 could be endocytosed efficiently by neutrophils and macrophages, and hID2 lost its protection function against colitis when neutrophils were depleted with an anti-Gr-1 antibody. hID2 decreased the mRNA levels of IL-6, IL-1β and TNF-α in lipopolysaccharides (LPS)-stimulated neutrophils and efficiently inhibited the activation of NF-κB signalling pathway in neutrophils. Interestingly, hID2 showed a synergistic role in inhibition of NF-κB activation with pyrrolidine dithiocarbamic acid (PDTC), an inhibitor of NF-κB activation. Therefore, this study demonstrated the potential use of hID2 to treat UC, and hID2 protein might be a promising anti-inflammatory agent that targets the NF-κB signalling pathway in neutrophils. |
| format |
article |
| author |
Jie Ren Dong Yan Yichun Wang Jiaojiao Zhang Min Li Wancheng Xiong Xueqian Jing Puze Li Weidong Zhao Xiwen Xiong Minna Wu Genshen Zhong |
| author_facet |
Jie Ren Dong Yan Yichun Wang Jiaojiao Zhang Min Li Wancheng Xiong Xueqian Jing Puze Li Weidong Zhao Xiwen Xiong Minna Wu Genshen Zhong |
| author_sort |
Jie Ren |
| title |
Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils |
| title_short |
Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils |
| title_full |
Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils |
| title_fullStr |
Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils |
| title_full_unstemmed |
Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils |
| title_sort |
inhibitor of differentiation-2 protein ameliorates dss-induced ulcerative colitis by inhibiting nf-κb activation in neutrophils |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/fbab3ce285ee45ada945b4a9d7a958f9 |
| work_keys_str_mv |
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| _version_ |
1718445128955199488 |