Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protease-Activated Receptor-2 (PAR2) has been implicated through genetic knockout mice with cytokine regulation and arthritis development. Many studies have associated PAR2 with inflammatory conditions (arthritis, airways inflammation, IBD) and key events in tumor progression (angiogenesis, metastasis), but they have relied heavily on the use of single agonists to identify physiological roles for PAR2. However such probes are now known not to be highly selective for PAR2, and thus precisely what PAR2 does and what mechanisms of downstream regulation are truly affected remain obscure. Effects of PAR2 activation on gene expression in Human Embryonic Kidney cells (HEK293), a commonly studied cell line in PAR2 research, were investigated here by comparing 19,000 human genes for intersecting up- or down-regulation by both trypsin (an endogenous protease that activates PAR2) and a PAR2 activating hexapeptide (2f-LIGRLO-NH(2)). Among 2,500 human genes regulated similarly by both agonists, there were clear associations between PAR2 activation and cellular metabolism (1,000 genes), the cell cycle, the MAPK pathway, HDAC and sirtuin enzymes, inflammatory cytokines, and anti-complement function. PAR-2 activation up-regulated four genes more than 5 fold (DUSP6, WWOX, AREG, SERPINB2) and down-regulated another six genes more than 3 fold (TXNIP, RARG, ITGB4, CTSD, MSC and TM4SF15). Both PAR2 and PAR1 activation resulted in up-regulated expression of several genes (CD44, FOSL1, TNFRSF12A, RAB3A, COPEB, CORO1C, THBS1, SDC4) known to be important in cancer. This is the first widespread profiling of specific activation of PAR2 and provides a valuable platform for better understanding key mechanistic roles of PAR2 in human physiology. Results clearly support the development of both antagonists and agonists of human PAR2 as potential disease modifying therapeutic agents.
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PMID:Profiling gene expression induced by protease-activated receptor 2 (PAR2) activation in human kidney cells. 2107 96

Out of 28 patients with inflammatory bowel disease in 11 (39.3%) revealed the presence of autoantibodies to gastric parietal cells. Appointment of MSC and infliximab did not lead to a reduction in antibody levels, in fact, in 6 (21.4%) patients had a further increase in the content of mentioned autoantibodies. Identification of autoantibodies to gastric parietal cells is considered as adherence to IBD autoimmune gastritis (formation of a systemic process) that requires use of corticosteroids. Transplantation of mesenchymal stromal cells in IBD reduces enhanced circulation of autoantibodies against antigens of neutrophils cytoplasmic structures, thereby reducing the severity of autoimmune reactions. Transplantation of MSCs reduces autoaggression in patients with ulcerative colitis, reducing the autoreactive clone of B lymphocytes (CD19+CD5+). Analysis effectiveness of the therapy. Transplantation of MSCs in IBD has a systemic immunoregulatory effect: on the one hand, stimulates oppressed cytokine synthesis, on the other--reduses the intensity of the autoimmune reactions and activity of pathological processes. Infliximab selectively blocks TNF-alpha, without affecting other proinflammatory cytokines.
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PMID:[The immune status changes in patients with inflammatory bowel disease under the influence of mesenchymal stromal cells and infliximab therapy]. 2262 69

One of the key links of pathological inflammatory process is the formation factors of adhesion. They play a leading role in the formation of inflammatory infiltration of the mucosa of the colon. Changes in the levels factors of adhesion under the influence of biological therapy are not well understood. In this regard, the aim of our study was to investigate the influence of biological therapy (infliximab, mesenchymal stromal cells) on the level of adhesion molecules in patients with IBD. Investigated the role of adhesion molecules to evaluate the effectiveness of treatment in this group of patients. Was examined 30 patients with IBD. Of these, 16 patients with ulcerative colitis (UC) and 14 patients with Crohn's disease (CD). Of these, 16 patients received infliximab 5 mg/kg body weight, 14 patients with IBD who underwent a comprehensive anti-inflammatory therapy with the introduction of MSC culture. Before and after treatment with infliximab, MSC transplantation was carried out a study of the clinical blood test, CRP, determined by the level of adhesion molecule L-selectin, E-selectin, P-selectin, integrin - sVCAM-1 in serum by ELISA Under the influence of infliximab for all IBD patients had significantly lower levels of P-selectin, E-selectin, integrin - sVCAM-1. In the group of patients after MSC transplantation rates of P-selectin, E-selectin was significantly decreased and the level of integrin - sVCAM-1 decreased slightly. The level of L-selectin in patients both after MSC transplantation and therapy with infliximab is practically not reduced, which serves as a reflection of chronic autoimmune inflammation, and the basis for long-term use of biological therapy in IBD. Adhesion molecule P-selectin, E-selectin, integrin - sVCAM-1 decreased more rapidly under the influence of infliximab in patients with IBD because of the mechanism of drug action (suppression of the synthesis of core inflammatory cytokine TNF-alpha). After transplantation of MSCs P-selectin, E-selectin, integrin - sVCAM-1 decreased more slowly due to the fact that the maximum positive effect of MSCs developed after 1 month. P-selectin, E-selectin, L-selectin, integrin - sVCAM-1 are the modern markers of inflammation and can be used to evaluate the effectiveness of biological therapy in IBD and the prognosis of the disease.
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PMID:[The role of adhesion molecules for assessing the effectiveness of biological treatment of patients with inflammatory bowel disease]. 2340 83

Inflammatory bowel diseases (IBD are a collection of diseases associated with chronic inflammation in the intestinal mucosa and/or transmural involvement. IBD is divided into two main categories Crohn's disease (CD and ulcerative colitis (UC. While there is no cure for IBD, current therapies can only reduce the inflammatory process that causes the signs and symptoms of IBD and hopefully induce long-term remission. Improved treatment modalities for the complex IBD are still evolving. The increased understanding of the underlying immunopathology has helped identify new targeted treatment options in particular the use of stem cell treatments that are capable of modulating the immune system. Haematopoietic stem cells (HSC and mesenchymal stromal cells (MSC therapy are both being investigated as a treatment for IBD. MSC therapy is well tolerated and associated with minimal established side-effects compared to HSC therapy, which involves ablative chemotherapy. Currently, such stem cell therapy is not a standard of care regimen for IBD. However, it may potentially become the next generation treatment of choice, especially for severe refractory IBD patients.
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PMID:Management of Inflammatory Bowel Disease Using Stem Cell Therapy. 2621 28

Owing to the recent progress in regenerative medicine technology, clinical trials that harnessed the regeneration and immune modulation potentiality of stem cells for treating IBD have shown promising results. We investigated the feasibility and utility of intraluminal endoscopic transplantation of rat MSC sheets in murine models of experimental colitis for targeted delivery of stem cells to lesions. We isolated adipose-derived mesenchymal stem cells (AD-MSC) and bone marrow-derived mesenchymal stem cells (BM-MSC) from EGFP-transgenic rats and fabricated the cells in sheet forms using temperature-responsive culture dishes. The MSC sheets were endoscopically transplanted to the inflamed area in electrocoagulation and DNBS colitis model. The effect of the transplantation was verified using endoscopic scoring and histological analysis. In the electrocoagulation model, the AD-MSC group showed significantly decreased ulcer size in the transplanted regions. In the DNBS colitis model, the AD-MSC group showed decreased inflammation and colitis in the transplanted regions. Histologic analysis showed that the MSC sheets had successfully attached to the inflamed mucosa in both the electrocoagulation and DNBS colitis model. Our results show that endoscopic transplantation of MSC sheets could be a new effective mode of stem cell therapy for IBD treatment.
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PMID:Endoscopic Transplantation of Mesenchymal Stem Cell Sheets in Experimental Colitis in Rats. 3005 22