LL202 protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting MAPK/AP-1 signaling
| Autor: | Zhiyu Li, Qinglong Guo, Kai Zhao, Yue Zhao, Yuan Gao, Yujie Huang, Na Lu, Yang Hu |
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| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine MAPK/ERK pathway Lipopolysaccharide colitis THP-1 Cells Interleukin-1beta Nitric Oxide Synthase Type II Pharmacology Mice chemistry.chemical_compound 0302 clinical medicine CD11b Antigen Neovascularization Pathologic biology Dextran Sulfate Nitric oxide synthase Oncology 030220 oncology & carcinogenesis Myeloperoxidase Cytokines Female Tumor necrosis factor alpha medicine.symptom Research Paper Signal Transduction MAP Kinase Signaling System p38 mitogen-activated protein kinases Active Transport Cell Nucleus Inflammation LL202 03 medical and health sciences medicine Animals Humans RNA Messenger Colitis Peroxidase Flavonoids Interleukin-6 Tumor Necrosis Factor-alpha business.industry AP-1 medicine.disease Mice Inbred C57BL Transcription Factor AP-1 030104 developmental biology Gene Expression Regulation chemistry Immunology biology.protein business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Yuan Gao 1, * , Yujie Huang 1, * , Yue Zhao 1 , Yang Hu 1 , Zhiyu Li 2 , Qinglong Guo 1 , Kai Zhao 1 , Na Lu 1 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China 2 School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China * These authors have contributed equally to this work Correspondence to: Na Lu, email: luna555@163.com Kai Zhao, email: cpuzhaokai@163.com Keywords: LL202, colitis, inflammation, AP-1 Received: June 09, 2016 Accepted: August 26, 2016 Published: August 31, 2016 ABSTRACT LL202, a newly-synthesized flavonoid derivative, has been reported to inhibit inflammatory-induced angiogenesis. However, the exact role of LL202 in inflammation along with its mechanism has not been explored. In this study, we investigated the anti-inflammatory effect of LL202 on intestinal inflammation by establishing dextran sulfate sodium (DSS)-induced experimental colitis. LL202 attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. The inflammatory cells infiltration, myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities were decreased by LL202 in a dose-dependent manner. LL202 reduced the production of pro-inflammatory cytokines in serum and colon of DSS-induced mice as well. Mechanically, LL202 could decrease the expression and nuclear translation of AP-1 to protect against DSS-induced colitis. In lipopolysaccharide (LPS)-induced THP-1 cells, LL202 markedly decreased the secretion, mRNA level and protein expression of IL-1β, IL-6 and TNF-α via inhibiting ERK/JNK/p38 MAPK pathways and the nuclear translocation of AP-1. Furthermore, these findings were confirmed in LPS-induced bone marrow derived macrophages (BMDM). In conclusion, our study demonstrated that LL202 could exert its anti-inflammatory effect via inhibiting MAPK/AP-1 signaling, which suggested that LL202 might be a potential effective drug for the treatment of inflammatory bowel diseases. |
| Databáze: | OpenAIRE |
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