Targeting TGF-beta1 by employing a vaccine ameliorates fibrosis in a mouse model of chronic colitis

Inflammatory Bowel Diseases
Yanbing MaZhikang Peng

Abstract

Intestinal fibrosis and stricture formation are major complications of inflammatory bowel disease (IBD), for which there are currently few effective treatments. We sought to investigate whether targeting transforming growth factor-beta1 (TGF-beta1), a key profibrotic mediator, with a peptide-based virus-like particle vaccine would be effective in suppressing intestinal fibrosis by using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis. The vaccine was prepared by inserting a peptide derived from mouse TGF-beta1 into a carrier hepatitis B core antigen using gene recombination methods. Chronic colitis was induced in BALB/c mice by 8 weekly TNBS administrations. Mice were subcutaneously injected with vaccine, carrier, or phosphate-buffered saline (PBS) in 2 separate studies: either before or after acute inflammatory responses commenced. Sera from vaccinated mice exhibited significantly elevated levels of TGF-beta1-specific immunoglobulin G (IgG), which inhibited TGF-beta1-induced luciferase production in mink lung epithelial cells. In the chronic colitis model, mice receiving vaccine showed improved body weight gain and significantly reduced colonic collagen deposition. Hematoxylin and eosin stai...Continue Reading

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Citations

Mar 9, 2013·American Journal of Respiratory Cell and Molecular Biology·Yanbing MaZhikang Peng
Feb 26, 2011·World Journal of Gastroenterology : WJG·Walter E CromerJ Steven Alexander
Mar 1, 2012·World Journal of Gastroenterology : WJG·Ferenc Sipos, Orsolya Galamb
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Aug 13, 2011·Free Radical Research·Magdalena L Circu, Tak Yee Aw
Mar 9, 2019·Current Pharmaceutical Design·Marjorie ArgolloSilvio Danese
Jun 9, 2020·Inflammatory Bowel Diseases·Bin LiuJi-Yu Li
Aug 11, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Florian RiederClaudio Fiocchi
Jul 18, 2020·Inflammatory Bowel Diseases·Calen A SteinerPeter D R Higgins
Aug 22, 2017·Frontiers in Medicine·Renata CurciarelloThomas T MacDonald
May 16, 2020·Journal of Digestive Diseases·Bo YangJie Wang
Dec 31, 2019·Journal of Immunology Research·Qingdong Guan
May 11, 2019·Rheumatology International·Sakir AhmedVikas Agarwal
Jan 8, 2021·Cellular & Molecular Immunology·Morten Orebo HolmströmMads Hald Andersen
Apr 26, 2021·Pharmacology & Therapeutics·Xuhui TongDapeng Chen
May 17, 2021·Immunological Reviews·Jie WangFlorian Rieder

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