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Crohn's disease and ulcerative colitis represent two distinct forms of inflammatory bowel diseases (IBD). In this paper, we discuss how immunological mechanisms contribute to the pathogenesis of IBD. Intestinal homeostasis is sustained by various kinds of cells, such as epithelial cells, lymphocytes, antigen presenting cells, and other innate immune cells. We pay special attention to intestinal CD14+ macrophages. Intestinal macrophages play a central role in the regulation of immune responses against commensal bacteria. In the physiological condition, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines. We identified a unique macrophage subset of IBD in the human intestine, which expressed both macrophage (CD14, CD33, CD68) and dendritic cell (DC) markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as interleukin (IL)-23 and tumor necrosis factor (TNF)-α. In addition, the CD14+ macrophages contributed to interferon (IFN)-γ production rather than IL-17 production by lamina propria mononuclear cells dependent on IL-23. We discuss herein this IL-23/IFN-γ-positive feedback loop in IBD patients. We also discuss IFN-γ and IL-17 production from mucosal T cells and natural killer (NK) cells. Here, we show our recent findings about the plasticity of T helper cells in colitis. Th17 cells express T-bet, and finally lose the expression of retinoic acid-related orphan receptor (ROR) γt, the master regulator of Th17 cells, and are differentiated 'alternative Th1 cells.' In addition to Th1 cells, mucosal NK cells are also important sources of IFN-γ. Some of our ideas may be provocative, but we hope this review paper will provide new and firm understanding of the pathogenesis of IBD. [ABSTRACT FROM AUTHOR]

Understanding of the pathophysiology of inflammatory bowel disease (IBD) is constantly evolving and, recently, a number of biologic agents that selectively target specific molecules or pathways to correct the imbalance of the gut immune system have been developed. Among them, an antibody to tumor necrosis factor (anti-TNF) is the first developed drug which has dramatically improved the management of patients with IBD. However, more than one-third of IBD patients do not respond to medications, and there is the problem of antibody formation. Therefore, enormous efforts have been made into the development of novel anti-cytokines and stem cell injection as an alternative to has been made. However, the efficacy and safety of stem cell treatment are under investigation. Some studies have reported very promising data; however, others have shown conflicting results. In addition, most trials involved a very small number of subjects and did not compare stem cell treatment with anti- TNF. The present paper reviews the function and therapeutic mechanism of stem cells for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Background/Aims: Double balloon enteroscopy (DBE) allows both diagnosis and therapeutic maneuvers in the small bowel. Its use was pioneered in Europe and Asia but there remains a relative paucity of literature from North America. Our aim in this study was to determine diagnostic and therapeutic yield in a North American setting. Methods: A five-year retrospective analysis of all patients undergoing DBE at a single tertiary care North American hospital was performed. Results: Four-hundred fifty-seven procedures, 265 anterograde and 192 retrograde, were performed on 335 patients. The most common indications were obscure gastrointestinal bleeding, small bowel obstruction, and suspected masses and mucosal abnormalities. Total enteroscopy was achieved in 19 of the 89 patients who had both anterograde and retrograde procedures. Overall diagnostic yield in the determination of cause of symptoms or previous imaging was 52%. The most common causes of obscure bleeding were small bowel ulcers (10%), vascular lesions (25%) and neoplasms (10%). The most common causes of small bowel obstruction were strictures, some of which underwent dilation. Other therapeutic interventions included polypectomy, retrieval of retained capsules, stent retrievals and percutaneous enteral jejunostomy tube placement. Overall complication rates were very low (0.6%) and included medication reaction (n=1), scope dysfunction (n=1) and perforation (n=1). Conclusions: DBE can be performed safely and with good diagnostic yield in a single referral center in North America. [ABSTRACT FROM AUTHOR]

Background/Aims: Parthenolide (PT) is responsible for the bioactivities of Feverfew. Besides its potent anti-inflammatory effect, this compound has recently been reported to induce apoptosis in cancer cells. Unfortunately, many of the therapies that use 5-fluorouracil (5-FU) alone or in combination with other agents are likely to become ineffective due to drug resistance. In the present study, we investigate the antitumor effect of PT combined with 5-FU on colorectal cancer cells. Methods: SW480 cell was employed as a representative of human colorectal carcinoma (CRC) cells. We performed MTT, annexin-V assay, and Hoechst 33258 staining to measure the synergistic effect. Western blotting was used to demonstrate apoptotic pathway. Results: Our result demonstrated that PT inhibited the viability of colorectal cancer cells and had synergistic anti-proliferation in combination with 5-FU. After combined treatment of 5-FU and PT, enhanced apoptotic cell death is observed using annexin-V FITC assay and it was revealed by the condensed chromatin and fragmented DNA. Compared with 5-FU or PT alone, the apoptosis of colorectal cancer cells treated with PT and 5-FU enhanced the activation of caspase-8, caspase-3. Conclusions: Combined treatment with PT may offer an efficacious strategy to overcome 5-FU resistance in certain CRC cells. [ABSTRACT FROM AUTHOR]