Intestine epithelial cells

Non-neuronal cells (including astrocytes, mechan-osensory hair cells, macrophages, keratinocytes, endothelial cells of the vascular system, muscle cells, lymphocytes, intestinal epithelial cells and various cell-types of the lungs)... 

Growth inhibition by TGF- 3, associated with inhibition of c-myc, cdks, reduction in cyclin D1 levels, and inhibition of cdk-4-associated Rb kinase activity, as well as induction of cdk inhibitors pi5 and p27, has been noted in intestinal epithelial cells. Loss of responsiveness to growth inhibition from TGF- 3 occurs in many cell types including breast, colorectal carcinoma, and pancreatic carcinoma cells. Mutational inactivation of T 3RH represents one mechanism of this process, which in many cases, leads to the development of gastrointestinal cancer. Thirteen percent of colorectal carcinomas are thought to be associated with a replication error (RER) or microsatellite instability phenotype. Subsequent inactivation of T 3RII and... 

Figure 5. Diagrammatic representation of the cytoskeleton in the apical region of the intestinal epithelial cell (enterocyte). (This diagram is from data previously published for example, see Mooseker, 1985.)...

Bundles of parallel actin filaments with uniform polarity. The microvilli of intestinal epithelial cells (enterocytes) are packed with actin filaments that are attached to the overlying plasma membrane through a complex composed of a 110-kD protein and calmodulin. The actin filaments are attached to each other through fimbrin (68 kD) and villin (95 kD). The actin bundles that emerge out of the roots of microvilli disperse horizontally to form a filamentous complex, the terminal web, in which several cytoskeletal proteins, spectrin (fodrin), myosin, actinin, and tropomyosin are present. Actin in the terminal web also forms a peripheral ring, which is associated with the plasma membrane on the lateral surfaces of the enterocyte (see Figure 5, p. 24). 

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

To correctly predict overall oral absorption, drug metabolism in intestinal epithelial cells by cytochrome P450 enzymes should also be considered. The prediction of drug metabolism has already been covered in detail in Chapter 18. 

Resistance to phagocytosis is sometimes associated with specific components of the cell wall and/or with the presence of capsules surrounding the cell wall. Classic examples of these are the M-proteins of the streptococci and the polysaccharide capsules of pneumococci. The acidic polysaccharide K-antigens of Escherichia coli and Sal typhi behave similarly, in that (i) they can mediate attachment to the intestinal epithelial cells, and (ii) they render phagocytosis more difficult. Generally, possession of an extracellular capsule will reduce the likelihood of phagocytosis. 

Particular strains of salmonellae (section 4.2) such as Sal. typhi, Sal. paratyphi and Sal. typhimurium are able not only to penetrate into intestinal epithelial cells and produce exotoxins but also to penetrate beyond into subepithelial tissues. These organisms therefore produce, in addition to the usual symptoms of salmonellosis, a characteristic systemic disease (typhoid and enteric fever). Following recovery frxm such infection the organism is commonly found associated with the gall bladder, hi this state, the recovered person will excrete the organism and form a reservoir for the infection of others. 

KOBAYASHI Y, SUZUKI M, SATSU H, ARAI S, KARA Y, SUZUKI K, MIYAMOTO Y, SHIMIZU M (2000) Green tea polyphenols inhibit the sodiiun-dependent glucose transporter of intestinal epithelial cells by a competitive mechanism. JAgric Food Chem. 48 5618-23. 

Production of Mucosal Damage 2.3.1.2.1 Cell culture Stimulated neutrophils are known to be cytotoxic to cells in vitro (Dull et al., 1987 Dallegri et al., 1990 Grisham et al., 1990b). Several in vitro systems have been used to demonstrate oxidative damage to intestinal cells. Xanthine/XO increased Cr release and decreased [ H]thymidine uptake by IEC-18 small intestinal epithelial cell monolayers in a dose-dependent manner (Ma et al., 1991). Rat enterocytes show decreased trypan blue exclusion and increased protein release when incubated with neutrophils stimulated... 

Cell culture Damage to small intestinal epithelial cells by XO can be prevented by SOD and desferrioxamine (Ma et al., 1991), whilst that to rat enterocytes, CaCo cells or rabbit colonic epithelial cells by XO can be decreased by catalase (Baker and Baker, 1990 Baker and Campbell, 1991 Kawabe etal., 1992). 

Ma, T.Y., Hollander, D., Freeman, D., Nguyen, T. and Krugliak, P. (1991). Oxygen free radical injury of IEC-18 small intestinal epithelial cell monolayers. Gastroenterology 100, 1533-1543. 

An alteration in the inflammatory response regulated by intestinal epithelial cells may also contribute to development of IBD. This may involve inappropriate processing of antigens presented to the GI epithelial cells.3 The inflammatory response in IBD may actually be directed at bacteria that normally colonize... 

Shigella strains invade intestinal epithelial cells with subsequent multiplication, inflammation, and destruction.8 The organism infects the superficial layer of the gut, rarely penetrates beyond the mucosa, and seldom invades the bloodstream. However, bacteremia can occur in malnourished children and I immunocompromised patients. 

Wurbel MA, Philippe JM, Nguyen C, et al. The chemokine TECK is expressed by thymic and intestinal epithelial cells and attracts double- and single-positive thymocytes expressing the TECK receptor CCR9. Eur J Immunol 2000 30 262-271. 

Wils, P. Wamery, A. Phung-Ba, V. Legrain, S. Scherman, D., High lipophilicity decreases drug transport across intestinal epithelial cells, J. Pharmacol. Exp. Ther. 269, 654-658 (1994). 

Figure 5 Parallel transcellular and paracellular pathways through intestinal epithelial cell monolayer.

G Wilson, IF Hassan, CJ Dix, I Williamson, R Shah, M Mackay. Transport and permeability properties of human Caco-2 cells An in vitro model of the intestinal epithelial cell barrier. J Controlled Release 11 25-40, 1990. 

Figure 2 Comparison of intestinal epithelial cells in culture and in situ. (A) Human colon Caco-2 cells grown in culture for 16 days on a semiporous filter. (B) Epithelial layer of rat jejunum. AP, apical or luminal membrane B, basal or abluminal membrane BM, basement membrane G, goblet cell LS, lateral space mv, microvilli Nu, nucleus TJ, tight junction. Bars equal 10 pm. 

Artis, D., Potten, C.S., Else, K.J., Finkelman, F.D. and Grencis, R.K. (1999b) Trichuris muris. host intestinal epithelial cell hyperproliferation during chronic infection is regulated by interferon-y. Experimental Parasitology 92, 144-153. 

Blumberg, R.S., Terhorst, C., Bleicher, P., Macdermott, F.V., Allan, C.H., Landan, S.B., Trier, J.S. and Balk, S.P. (1991) Expression of a non-polymorphic MHC class I-like molecule, CDld, by human intestinal epithelial cells. Journal of Immunology 147, 2518-2524. 

Eckmann, C., Jung, EEC., Schurer-Maly, C., Panja, A., Wroblewska, E.M. and Kagnoff, M. (1993) Differential cytokine expression by human intestinal epithelial cell lines regulated expression of IL-8. Gastroenterology 105, 1689-1697. 

Song, F., Ito, K., Denning, T.L., Kuninger, D., Papaconstantinou, J., Gourley, W., Klimpel, G., Balish, E., Hokanson, J. and Ernst, P.B. (1999) Expression of the neutrophil chemokine KC in the colon of mice with enterocolitis and by intestinal epithelial cell lines effects of flora and proinflammatory cytokines. Journal of Immunology 162, 2275-2280. 

Stadnyk, A.W., Sisson, G.R. and Waterhouse, C.C.M. (1995) Ida is constitutively expressed in the rat intestinal epithelial cell line IEC-6. Experimental Cell Research 220, 298-303. 

Takeuchi, M., Nishizaki, Y., Sano, O., Ohta, T., Ikeda, M. and Kurimoto, M. (1997) Immunohistochemical and immuno-electron-microscopic detection of inter-feron-gamma-inducing factor ( interleukin 18 ) in mouse intestinal epithelial cells. Cell and Tissue Research 289, 499-503. 

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