Proliferation, intestinal epithelial cells

IL-4 induces an antiinflammatory effect by its ability to suppress production of proinflammatory cytokines (IL-1, TNFa, and IL-6) and to favor the release of IL-1RA. This antiinflammatory action is evident on activated monocytes and/or macrophages, namely the inhibition of IL-6 production. Indeed, not all target cells may be influenced in this way (e.g., IL-4 may be capable of regulating intestinal epithelial cell proliferation without altering the capacity of these cells to function in the inflammatory response by secreting IL-6). IL-4 and IFNy also synergistically increase total polymeric IgA receptor levels in human intestinal epithelial cells. ... 

McGee DW> Vitkus SJ. IL-4 enhances IEC-6 intestinal epithelial cell proliferation yet has no effect on IL-6 secretion. Clin Exp Immuno 1996 105 274-7. 

CDX2 CDX2-88 Homeobox family of intestine-specific transcription factor regulates proliferation and differentiation of intestinal epithelial cells Full length GDX2 BioCenex NA HIER... 

CDX-2 CDX-2 is a caudal type homeobox gene, which encodes a 33-kDa 311-amino-acid nuclear protein. C DX-2 is an intestine-specific transcription factor expressed in the early intestinal development stage supposed to be involved in the differentiation, adhesion, proliferation and apoptosis of intestinal epithelial cells. 

DuBois. Peroxisome Proliferator-Activated Receptor y and Transforming Growth Factor-P Pathways Inhibit Intestinal Epithelial Cell Growth by Regulating Levels ofTSC-22. EiolChem 278-. 7431-7438 (2003). 

The origin and fate of the intestinal epithelial cells have been traced using radioautography. The absorptive cell proliferates in the crypts of Lieberkiihn. The new cells migrate toward the apex of the villi where they are extruded. Cellular proliferation and cellular extrusion are not rigidly linked for example, irradiation blocks cellular proliferation but doesn t affect cellular extrusion, and the villi atrophy. In sprue the reverse occurs cellular proliferation persists, but cellular extrusion seems to be accelerated. 

Vitamin A (retinol) is a fat-soluble vitamin important for the maintenance of skin, bone, and blood vessels, as well as for the promotion of vision (Theodosiou et al. 2010). It is obtained from the diet either as all-trans-retinol, retinyl esters, or P-carotene (Blomhoff and Blomhoff 2006) and is stored in the liver (Moise et al. 2007). Vitamin A is converted to retinoic acid (RA), which is formed mainly through intracellular oxidative metabolism by retinal dehydrogenases (RALDHs) (Lampen et al. 2000). RA plays important roles in embryonic development, organogenesis, tissue homeostasis, cell proliferation, differentiation, and apoptosis (Theodosiou et al. 2010). In adult mammals, RALDH is found in intestinal epithelial cells (lECs) and gut associated-dendritic cells (DCs) from Peyer s patches and mesenteric lymph nodes (Iwata 2004, Coombes et al. 2007). Gut-associated DCs and lECs can metabolize vitamin A to RA in vitro (Lampen 2000), which indicates they may be a source of RA in gut mucosa. RA binds to two families of nuclear receptors, RA receptor (RAR) isotypes (a, p, and y) and retinoic X receptor (RXR) isotypes (a, p, and y). RAR and RXR form heterodimers and interact with retinoic acid response elements (RAREs) within the promoters of retinoic acid responsive genes (Blomhoff and Blomhoff 2006). RAR is ubiquitously expressed and up-regulated by RA. RXR also... 

The surface epithelial cells of the small intestine are renewed rapidly and regularly. It takes about two days for the cells of the duodenum to be renewed completely. As a result of its rapid renewal rate, the intestinal epithelium is susceptible to various factors that may influence proliferation. Exposure of the intestine to ionizing radiation and cytotoxic drugs (such as folic acid antagonists and colchicine) reduces the cell renewal rate. 

The intrinsic barrier of the gastrointestinal epithelium is characterized by intercellular junctions at the apical (luminal) side of differentiated epithelial cells, the so-called tight junctions (TJ), and the maintenance of epithelial integrity based on the balance between cellular proliferation and cell death, as described above. Barriers against drug absorption by the intracellular and paracellular routes, their modulation, and maintenance will be discussed in the following, with the focus on the intestinal epithelium. 

Other transcellular mechanisms of absorption include carrier-mediated transport and endocytic processes. Although it is well known that carrier-mediated transport systems exist for di- and tripeptides in the intestine, there is still no evidence for carrier-mediated transport of peptides across the vaginal mucosa, although prostaglandins have been demonstrated to utilize such a mechanism. Although there must be some type of endocytic transport of endogenous peptides into the epithelial cells in order to regulate proliferation, no receptor-mediated or bulk-fluid mechanisms have been reported. 

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