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Interactions Between Immune Cells of Intestinal Mucosa or Peripheral Blood With the Extracellular Matrix in Inflammatory Bowel Disease (IBD)

2014-07-24 14:12:37 | BioPortfolio

Summary

The purpose of this study is to examine the effects of different environmental factors on immune cells in patients with IBD.

Description

Background: Inflammatory bowel diseases, comprised of Crohn's Disease (CD) and ulcerative colitis (UC) are idiopathic disorders caused due to immunological, genetic, and environmental factors. These disorders are fairly common (in the US, there are 11 cases of CD and 7 cases of UC for every 100,000 people). The frequency of IBD, especially CD, are constantly rising (1). Clinical symptoms include diarrhea, rectal bleeding, abdominal pain, intestinal obstructions, and fistulas in CD. There are also systemic manifestations such as fever, weight loss, and anemia. The current hypothesis of IBD pathogenesis is an aberrant, ongoing, uncontrolled inflammatory response of the intestine, caused by commensal microbiota. The inflammatory response in IBD is mediated by T cells; in CD the pathologic lymphocytes are CD4 cells of Th1 type, while UC is considered an atypical Th2 response (2). CD4 T cells have a major role in initiation of inflammatory response in the gut, as well as a role in propagation and control of the inflammation.

Chemokines are low-molecular weight cytokines with chemoattractant capacity, and have a role in many inflammatory disorders. The chemokine CXCL12 is considered to be constitutively expressed (3). Our group found increased expression of CXCL12 in IBD (REF?). This finding suggests that CXCL12 might have a role in inflammatory processes of the gut.

Understanding phenotypical and functional differences of lymphocytes in mucosal homeostasis and IBD, elucidation of factors causing these differences, and recognition of causes for increased CXCL12 expression, will enable to increase knowledge of IBD; as well as lead to development of future therapeutic interventions in IBD.

Research Goals: To examine the effects of different environmental factors (cytokines, chemokines, extracellular matrix moieties) on immune cells from peripheral or intestinal source (in homeostasis or IBD) in terms of phenotypical and functional parameters.

Methods: 15 ml peripheral blood will be obtained from all participants. T lymphocytes will be isolated for the different experiments. Methods will include: Migration towards chemokines using the Transwell assay, proliferation will be assessed by either BrdU or thymidine incorporation, cytokine secretion will be determined using ELISA, phenotypical characterization will be done using flow cytometry and adhesion assays.

Ages: Adults and children aged 10-80. Research group: Approximately 40 patients (adults and children) suffering from IBD will be enrolled.

Control group: Approximately 100 controls will be enrolled in the research.

Study Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Conditions

Inflammatory Bowel Disease

Location

Dep. of Gastroenterology, Tel Aviv medical center
Tel Aviv
Israel

Status

Recruiting

Source

Tel-Aviv Sourasky Medical Center

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-07-24T14:12:37-0400

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Medical and Biotech [MESH] Definitions

An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed)

A species of Faecalbacterium, previously classified in the FUSOBACTERIUM genus, that is a major constituent of the GUT MICROBIOTA in healthy humans. It has anti-inflammatory activity and reduced numbers of this species occur in patients with INFLAMMATORY BOWEL DISEASES such as CROHN DISEASE.

Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.

A member of the S-100 protein family that is present at high levels in the blood and interstitial fluid in several infectious, inflammatory, and malignant disorders, including rheumatoid arthritis, inflammatory bowel disease, and cystic fibrosis. It is a complex of a light chain (CALGRANULIN A) and a heavy chain (CALGRANULIN B). L1 binds calcium through an EF-hand motif, and has been shown to possess antimicrobial activity.

A PRENATAL ULTRASONOGRAPHY finding of excessively dense fetal bowel due to MECONIUM buildup.

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