Oral delivery of staphylococcal nuclease ameliorates DSS induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular traps
Recent studies have revealed that neutrophil extracellular traps (NETs) may contribute directly to the initiation of ulcerative colitis (UC), a typical inflammatory bowel disease (IBD) characterized by mucosal damage. Staphylococcal nuclease (SNase), a nonspecific phosphodiesterase, has a strong abi...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651321002724 |
| _version_ | 1818438804579549184 |
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| author | Wanfa Dong Dan Liu Tingting Zhang Qi You Fengjie Huang Jie Wu |
| author_facet | Wanfa Dong Dan Liu Tingting Zhang Qi You Fengjie Huang Jie Wu |
| author_sort | Wanfa Dong |
| collection | DOAJ |
| description | Recent studies have revealed that neutrophil extracellular traps (NETs) may contribute directly to the initiation of ulcerative colitis (UC), a typical inflammatory bowel disease (IBD) characterized by mucosal damage. Staphylococcal nuclease (SNase), a nonspecific phosphodiesterase, has a strong ability to degrade DNA. Here we investigate whether intestinal NET degradation with an oral preparation of SNase can ameliorate dextran sulfate sodium (DSS)-induced UC in mice. SNase encapsulated with calcium alginate (ALG-SNase) was formulated using crosslinking technology with sodium alginate and calcium chloride. ALG-SNase were orally administered to DSS-induced UC mice, and their therapeutic efficacy was evaluated. The expression of inflammatory cytokines and biomarkers of NETs was also assessed, as well as the intestinal permeability in mice. The results showed that ALG-SNase nanoparticles were successfully prepared and delivered to the colon of UC mice. In addition, oral administration of ALG-SNase nanoparticles decreased NET levels in the colon and effectively alleviated the clinical colitis index and tissue inflammation in UC mice. Moreover, the SNase nanoparticles reduced intestinal permeability and regulated the expression of proinflammatory cytokines. Furthermore, the markers of NETs were strongly correlated with the expression levels of tight junction proteins in colon tissue. In conclusion, our data showed that oral administration of ALG-SNase can effectively ameliorate colitis in UC mice via NET degradation and suggested SNase as a candidate therapy for the treatment of UC. |
| first_indexed | 2024-12-14T17:46:23Z |
| format | Article |
| id | doaj.art-5f195ec85b8f4a26a392992d5a4a9a40 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-14T17:46:23Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-5f195ec85b8f4a26a392992d5a4a9a402022-12-21T22:52:44ZengElsevierEcotoxicology and Environmental Safety0147-65132021-06-01215112161Oral delivery of staphylococcal nuclease ameliorates DSS induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular trapsWanfa Dong0Dan Liu1Tingting Zhang2Qi You3Fengjie Huang4Jie Wu5College of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaCollege of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaCollege of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaCollege of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaCollege of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaCorrespondence to: China Pharmaceutical University, No. 639, Longmian Road, Jiangning District, Nanjing, Jiangsu 211198, China.; College of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaRecent studies have revealed that neutrophil extracellular traps (NETs) may contribute directly to the initiation of ulcerative colitis (UC), a typical inflammatory bowel disease (IBD) characterized by mucosal damage. Staphylococcal nuclease (SNase), a nonspecific phosphodiesterase, has a strong ability to degrade DNA. Here we investigate whether intestinal NET degradation with an oral preparation of SNase can ameliorate dextran sulfate sodium (DSS)-induced UC in mice. SNase encapsulated with calcium alginate (ALG-SNase) was formulated using crosslinking technology with sodium alginate and calcium chloride. ALG-SNase were orally administered to DSS-induced UC mice, and their therapeutic efficacy was evaluated. The expression of inflammatory cytokines and biomarkers of NETs was also assessed, as well as the intestinal permeability in mice. The results showed that ALG-SNase nanoparticles were successfully prepared and delivered to the colon of UC mice. In addition, oral administration of ALG-SNase nanoparticles decreased NET levels in the colon and effectively alleviated the clinical colitis index and tissue inflammation in UC mice. Moreover, the SNase nanoparticles reduced intestinal permeability and regulated the expression of proinflammatory cytokines. Furthermore, the markers of NETs were strongly correlated with the expression levels of tight junction proteins in colon tissue. In conclusion, our data showed that oral administration of ALG-SNase can effectively ameliorate colitis in UC mice via NET degradation and suggested SNase as a candidate therapy for the treatment of UC.http://www.sciencedirect.com/science/article/pii/S0147651321002724Ulcerative colitis (UC)Neutrophil extracellular traps (NETs)Staphylococcal nuclease (SNase)Calcium alginate |
| spellingShingle | Wanfa Dong Dan Liu Tingting Zhang Qi You Fengjie Huang Jie Wu Oral delivery of staphylococcal nuclease ameliorates DSS induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular traps Ecotoxicology and Environmental Safety Ulcerative colitis (UC) Neutrophil extracellular traps (NETs) Staphylococcal nuclease (SNase) Calcium alginate |
| title | Oral delivery of staphylococcal nuclease ameliorates DSS induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular traps |
| title_full | Oral delivery of staphylococcal nuclease ameliorates DSS induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular traps |
| title_fullStr | Oral delivery of staphylococcal nuclease ameliorates DSS induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular traps |
| title_full_unstemmed | Oral delivery of staphylococcal nuclease ameliorates DSS induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular traps |
| title_short | Oral delivery of staphylococcal nuclease ameliorates DSS induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular traps |
| title_sort | oral delivery of staphylococcal nuclease ameliorates dss induced ulcerative colitis in mice via degrading intestinal neutrophil extracellular traps |
| topic | Ulcerative colitis (UC) Neutrophil extracellular traps (NETs) Staphylococcal nuclease (SNase) Calcium alginate |
| url | http://www.sciencedirect.com/science/article/pii/S0147651321002724 |
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