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Intestinal Fibrosis (intestinal + fibrosis)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Targeting TGF-,1 by employing a vaccine ameliorates fibrosis in a mouse model of chronic colitis

INFLAMMATORY BOWEL DISEASES, Issue 6 2010
Yanbing Ma MSc
Abstract Background: 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-,1), 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. Methods: The vaccine was prepared by inserting a peptide derived from mouse TGF-,1 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. Results: Sera from vaccinated mice exhibited significantly elevated levels of TGF-,1-specific immunoglobulin G (IgG), which inhibited TGF-,1-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 staining and semiquantitative scoring indicated that vaccination even ameliorated colonic inflammation. Cytokine profile analysis revealed that levels of TGF-,1, interleukin (IL)-17, and IL-23 in vaccinated mouse colon tissues were decreased, and that percentages of IL-17-expressing CD4+ lymphocytes in mesenteric lymph node cells were reduced. Furthermore, Smad3 phosphorylation, a key event in TGF-, signaling, was decreased in colonic tissue in vaccinated mice. Conclusions: This TGF-,1 peptide-based vaccine, which suppressed excessive TGF-,1 bioactivity, may prevent the development of intestinal fibrosis and associated complications, presenting a novel approach in the treatment of IBD. (Inflamm Bowel Dis 2010) [source]

Medical therapy for Crohn's disease strictures

INFLAMMATORY BOWEL DISEASES, Issue 1 2004
Gert Van Assche MD
Abstract Intestinal fibrostenosis is a frequent and debilitating complication of Crohn's disease (CD), not only resulting in small bowel obstruction, but eventually in repeated bowel resection and short bowel syndrome. Over one third of patients with CD have a clear stenosing disease phenotype, often in the absence of luminal inflammatory symptoms. Intestinal fibrosis is a consequence of chronic transmural inflammation in CD. As in other organs and tissues, phenotypic transformation and activation of resident mesenchymal cells, such as fibroblasts and smooth muscle cells, underlie fibrogenesis in the gut. The molecular mechanisms and growth factors involved in this process have not been identified. However, it is clear that inflammatory mediators may have effects on mesenchymal cells in the submucosa and the muscle layers that are profoundly different from their action on leukocytes or epithelial cells. Transforming growth factor-beta (TGF-,), for instance, has profound anti-inflammatory activity in the mucosa and probably serves to keep physiologic inflammation at bay, but at the same time it appears to be driving the process of fibrosis in the deeper layers of the gut. Tumor necrosis factor, on the other hand, has antifibrotic bioactivity and pharmacologic inhibition of this cytokine carries a theoretical risk of enhanced stricture formation. Endoscopic management of intestinal strictures with balloon dilation is an accepted strategy to prevent or postpone repeated surgery, but careful patient selection is of paramount importance to ensure favorable long-term outcomes. Specific medical therapy aimed at preventing or reversing intestinal fibrosis is not yet available, but candidate molecules are emerging from research in the liver and in other organs. [source]

Targeting TGF-,1 by employing a vaccine ameliorates fibrosis in a mouse model of chronic colitis

INFLAMMATORY BOWEL DISEASES, Issue 6 2010
Yanbing Ma MSc
Abstract Background: 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-,1), 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. Methods: The vaccine was prepared by inserting a peptide derived from mouse TGF-,1 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. Results: Sera from vaccinated mice exhibited significantly elevated levels of TGF-,1-specific immunoglobulin G (IgG), which inhibited TGF-,1-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 staining and semiquantitative scoring indicated that vaccination even ameliorated colonic inflammation. Cytokine profile analysis revealed that levels of TGF-,1, interleukin (IL)-17, and IL-23 in vaccinated mouse colon tissues were decreased, and that percentages of IL-17-expressing CD4+ lymphocytes in mesenteric lymph node cells were reduced. Furthermore, Smad3 phosphorylation, a key event in TGF-, signaling, was decreased in colonic tissue in vaccinated mice. Conclusions: This TGF-,1 peptide-based vaccine, which suppressed excessive TGF-,1 bioactivity, may prevent the development of intestinal fibrosis and associated complications, presenting a novel approach in the treatment of IBD. (Inflamm Bowel Dis 2010) [source]

Medical therapy for Crohn's disease strictures

INFLAMMATORY BOWEL DISEASES, Issue 1 2004
Gert Van Assche MD
Abstract Intestinal fibrostenosis is a frequent and debilitating complication of Crohn's disease (CD), not only resulting in small bowel obstruction, but eventually in repeated bowel resection and short bowel syndrome. Over one third of patients with CD have a clear stenosing disease phenotype, often in the absence of luminal inflammatory symptoms. Intestinal fibrosis is a consequence of chronic transmural inflammation in CD. As in other organs and tissues, phenotypic transformation and activation of resident mesenchymal cells, such as fibroblasts and smooth muscle cells, underlie fibrogenesis in the gut. The molecular mechanisms and growth factors involved in this process have not been identified. However, it is clear that inflammatory mediators may have effects on mesenchymal cells in the submucosa and the muscle layers that are profoundly different from their action on leukocytes or epithelial cells. Transforming growth factor-beta (TGF-,), for instance, has profound anti-inflammatory activity in the mucosa and probably serves to keep physiologic inflammation at bay, but at the same time it appears to be driving the process of fibrosis in the deeper layers of the gut. Tumor necrosis factor, on the other hand, has antifibrotic bioactivity and pharmacologic inhibition of this cytokine carries a theoretical risk of enhanced stricture formation. Endoscopic management of intestinal strictures with balloon dilation is an accepted strategy to prevent or postpone repeated surgery, but careful patient selection is of paramount importance to ensure favorable long-term outcomes. Specific medical therapy aimed at preventing or reversing intestinal fibrosis is not yet available, but candidate molecules are emerging from research in the liver and in other organs. [source]

Review article: anti-fibrotic agents for the treatment of Crohn's disease , lessons learnt from other diseases

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010
H. SZABÒ
Summary Background, The current therapies for Crohn's disease (CD) are mainly focused on blockade of inflammation. Fibrosis remains one of the major complications of CD often leading to surgery, affecting patients' quality-of-life. Aim, To summarize the published data regarding the potential anti-fibrotic role of drugs commonly used in CD and the most effective anti-fibrotic drugs used in other diseases evaluating their potential use to treat intestinal fibrosis in CD. Methods, A literature search was performed in the PubMed, Medline, Cochrane and EMBASE databases, considering in vitro, animal and human studies on fibrosis in inflammatory bowel disease and other similar chronic pathologies. Results, Treatment of fibrosis in CD is limited to surgery or endoscopic dilatation, although some of the drugs currently used may have anti-fibrotic activity. In other diseases, anti-fibrotic agents are already used or are in preclinical or clinical trials. ACE inhibitors, Angiotensin Receptor Blockers, and HMG-CoA inhibitors merit further investigation in CD because of their role in preventing fibrosis in cardiovascular and renal diseases. Conclusions, Anti-fibrotic drugs are under evaluation or already used in clinical practice in other chronic inflammatory diseases. In CD, there is a great need for investigation into agents that may prevent, reduce or reverse intestinal fibrosis. Aliment Pharmacol Ther,31, 189,201 [source]