Intestinal epithelial cells functions

The mechanisms whereby mast cells enhance host protection to H. polygyms and T. spiralis (and whether these are related to the leak-lesion hypothesis) have not yet been fully defined. Certainly, mast cells contribute to intestinal inflammation during infection through the secretion of a range of cytokines (Gordon et al., 1990) and vasoactive substances (see above). In addition, the release of mast cell proteases are known to increase enterocyte permeability to macromolecules in the rat intestine (Scudamore et al., 1995) and regulate epithelial cell functions at other mucosal sites (Cairns and Walls, 1996). 

The main reasons for the popularity of the Caco-2 cell line are that the cells are easy to maintain in culture, and they develop unusually high degree of differentiation spontaneously under standard culture conditions. In fact, Caco-2 is the only human intestinal cell line that has been found so far spontaneously to undergo functional enterocytic differentiation. The cells exhibit a good reproducibility, robustness and functional properties of human intestinal epithelial cells. The model has proved capable of predicting the oral absorption of a variety of drug compounds [see references in 10]. 

Menkes disease, an X-linked recessive condition, is caused by mutations in the gene encoding a Cu efflux protein. Cells from an affected individual accumulate high concentrations of Cu " that cannot be released from the cell. The symptoms result from functional Cu deficiency inasmuch as Cu absorbed from the intestine becomes trapped in the intestinal epithelial cells and delivery to other tissues is inadequate. 

The illustration schematically shows a detail of the microvilli of an intestinal epithelial cell as an example of the structure and function of the components of the cytoskeleton (see also Cl). 

INTESTINE Characterization of a membrane potassium ion conductance in intestinal secretory cells using whole cell patch-clamp and calcium-sensitive dye techniques, 192, 309 isolation of intestinal epithelial cells and evaluation of transport functions, 192, 324 isolation of enterocyte membranes, 192, 341 established intestinal cell lines as model systems for electrolyte transport studies, 192, 354 sodium chloride transport pathways in intestinal membrane vesicles, 192, 389 advantages and limitations of vesicles for the characterization and the kinetic analysis of transport systems, 192, 409 isolation and reconstitution of the sodium-de-pendent glucose transporter, 192, 438 calcium transport by intestinal epithelial cell basolateral membrane, 192, 448 electrical measurements in large intestine (including cecum, colon, rectum), 192, 459... 

Human PepTl was initially cloned from intestine (92) and was found to be localized to the brush border of intestinal epithelial cells (93) and in SI segment of apical proximal tubules (94). PepTl transports (3-lactam antibiotics (95), antiviral drugs such as valacyclovir and valganciclovir (96), and the angiotensin converting enzyme inhibitor captopril (97). Polymorphisms have been reported, however little is known regarding their functional consequences (64). 

O Hara, A. M., O Regan, P., Fanning, A., O Mahony, C., MacSharry, J., Lyons, A., Bienenstock, J., O Mahony, L., and Shanahan, F. (2006). Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius. Immunology 118, 202-215. 

Intestinal mucosal cells also can activate mediators of inflammation. Intestinal epithelial cells express an array of cytokine receptors and produce a spectrum of immune mediators, suggesting that they play an integral role in mucosal innate and acquired immunity (Dwinell et al 1999). Consistent with those functions, human intestinal epithelial cells have been shown to upregu-late the expression and secretion of a variety of proinflammatory chemokines in response to infection with enteroinvasive pathogens or stimulation with proinflammatory cytokines. Epithelial cell-derived chemokines appear to act as mediators of intercellular communication between the epithelium and immune and inflammatory cells in the adjacent and underlying mucosa. 

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. ... 

The role of melanotransferrin has been recently elucidated by Kennard et al. [207] who demonstrated that this membrane bound iron binding protein is involved in the transferrin-independent uptake of iron in mammals but from iron-citrate and not from iron-transferrin complexes. This alternative iron uptake pathway may not function in the normal recirculation of iron within the body but might play a role during iron overload. On the other hand, rapidly proliferative tumor cells like melanocytes could use the alternative pathway to increase iron uptake. This independent system could also participate in the absorption of iron by intestinal cells that have no transferrin receptor on their lumenal surfaces [208], but express a transferrin-like GPI-linked iron-binding protein at the apical surface of fetal intestinal epithelial cells [209]. 

On the basis of the data reviewed in this chapter, it seems likely that there are functionally distinct pools of cholesterol in the intestinal epithelial cell that serve different metabolic functions. These pools are illustrated diagrammatically in the model of an epithelial cell shown in Fig. 14. Pool A is defined as having been derived largely from the uptake of luminal unesterified cholesterol (arrow 1) and serves as a major substrate for the CoA-dependent esterification reaction (arrow 2). The cholesterol esters that result from this reaction are incorporated into the hydro-phobic core of the chylomicron particle. Following cholesterol feeding there is a marked increase in apparent ACAT activity in the intestinal epithelium that seems to be related to an increase in the amount of intracellular cholesterol available to the enzyme under the in vitro conditions of the assay rather than to an increase in the... 

Another nuclear receptor, called FXR, is activated by the binding of bile acids. Expressed in hepatocytes and intestinal epithelial cells, FXR plays a key role in regulating the en-terohepatlc circulation of bile acids. Bile acid-activated FXR stimulates the expression of Intracellular bile acid-binding protein (I-BABP) and of transport proteins (e.g., ABCBll, NTCP) that mediate cellular export and Import of bile acids (see Figure 18-11). In contrast, active FXR represses the expression of cholesterol 7a-hydroxylase, thereby decreasing the synthesis of bile acids from cholesterol in the liver—another example of end-product Inhibition of a metabolic pathway. Both FXR and LXR function as heterodimers with the nuclear receptor RXR. 

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