Document Detail


A novel tylophorine analog W-8 up-regulates forkhead boxP3 expression and ameliorates murine colitis.
MedLine Citation:
PMID:  23142729     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Tylophorine and analogs are phenanthroindolizidine alkaloids, several of which have been reported to have anticancer, antiviral, and anti-inflammatory properties. However, their function in the immune system remains widely unknown. Transcription factor Foxp3 is critical for the development and function of Treg, which down-regulates the immune system and maintains tolerance to self-antigens. In the present study, we defined a novel tylophorine analog, W-8, enhanced TGF-β-induced Foxp3 expression at the mRNA and the protein levels. Interestingly, W-8 synergistically increased the level of TGF-β-induced p-Smad3 through inhibition of the AKT/mTOR pathway and enhanced the demethylation of the promoter region of the Foxp3 through inhibition of the ERK pathway and DNMT1 expression. Moreover, administration of W-8 suppressed TNBS-induced murine colitis and increased Tregs in lymphoid tissues. Finally, W-8 enhanced conversion of naïve T cells to Tregs in vivo. In summary, our results defined a novel compound that enhanced Foxp3 expression through transcriptional and epigenetic programs, and it might serve as a therapeutic agent for inflammatory diseases.
Authors:
Xianyi Meng; Yun Zhang; Zhenghu Jia; Xiaojing Huo; Xiangjun He; Gaofei Tian; Meng Wu; Ziwen Wang; Xinglong Zhou; Sidong Xiong; Xiaoming Gao; Zhenzhou Wu; Jihong Han; Liqing Zhao; Puyue Wang; Zhangyong Hong; Qingmin Wang; Zhinan Yin
Related Documents :
23071089 - Tob2 inhibits peroxisome proliferator-activated receptor γ2 expression by sequestering...
24371169 - Molecular characterization and expression analysis of fat mass and obesity-associated g...
20506119 - Egr1, egr2, and egr3 activate the expression of their coregulator nab2 establishing a n...
22960219 - Chicken fto gene: tissue-specific expression, brain distribution, breed difference and ...
24238219 - Expression analysis and in silico characterization of intronic long noncoding rnas in r...
24258459 - Chd1l is a novel independent prognostic factor for gastric cancer.
12148579 - Molecular changes in the early stage of colon carcinogenesis in rats treated with azoxy...
8605019 - Regulation of fatty acid synthase expression by cholesterol in human cultured cells.
19799979 - The korean traditional medicine gyeongshingangjeehwan inhibits adipocyte hypertrophy an...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-9
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  -     ISSN:  1938-3673     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*State Key Laboratories of Medicinal Chemical Biology, College of Life Sciences, and.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Identifiability of diffusion and sorption parameters from in situ diffusion experiments by using sim...
Next Document:  P-cadherin controls the differentiation of oral keratinocytes by regulating cytokeratin 1/10 express...