Cell line intestinal epithelial

VolSurf was also successfully applied in the literature to predict absorption properties [156] from experimental drug permeability data of 55 compounds [165] in Caco-2 cells (human intestinal epithelial cell line derived from a colorectal carcinoma) and MDCK cell monolayers (Madin-Darby canine kidney). In this interesting case, it was shown that models including counterions for charged molecules clearly show significantly better quality and overall performance. The final model was also able to correctly predict, to a great extent, the relative ranking of molecules from another Caco-2 permeability study by Yazdanian et al. ]166]. 

Recently, several strains of L. rhamnosus and L. delbrueckii were also observed to downregulate IL-8 production in HT-29 cells, an intestinal epithelial cell line (Wallace et al. 2003). Together with these findings, it appears that inhibition of IL-8 production may be part of the mechanism by which lactobacilli impart their welfare to the gut. This could explain their ability to treat intestinal disorders associated with high levels of IL-8. 

Cell Lines and Cell Culture. Intestinal epithelial Caco-2 cells was obtained from the American T3q>e Culture Collection (Manassas, VA) and cultured in minimum essential... 

K0/w as measured in the rat intestine [15,16], As with other examples that are available, as K0/w increases, the rate of absorption increases. One very extensive study [17-19] has examined in depth the physicochemical factors governing nonelectrolyte permeability for several hundred compounds. This study employed an in vitro preparation of rabbit gallbladder, an organ whose mucosal surface is lined by epithelial cells. The... 

The surface area in the luminal side of the small intestine per unit length of the serosal (blood) side is enormous in the proximal jejunum, and steadily decreases (to about 20% of the starting value [62]) in the distal portions of the small intestine. The surface area is increased threefold [69] by ridges oriented circumferentially around the lumen. Similar folds are found in all segments of the GIT, except the mouth and esophagus [66]. Further 4—10-fold expansion [62,69] of the surface is produced by the villi structures, shown schematically in Fig. 2.4. The layer of epithelial cells lining the villi structures separate the lumen from the circulatory system. Epithelial cells are made in the crypt folds of the villi, and take about... 

W Rubas, N Jezyk, GM Grass. Comparison of the permeability characteristics of a human colonic epithelial (Caco-2) cell line to colon of rabbit, monkey, and dog intestine and human drug absorption. Pharm Res 10 113-118, 1993. 

Gres, M. C. et al. (1998). Correlation between oral drug absorption in humans, and apparent drug permeability in TC-7 cells, a human epithelial intestinal cell line Comparison with the parental Caco-2 cell line. Pharm. Res. 15(5) 726-733. 

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. 

Some laboratories have found an alternative to the short-term cultures by using cell lines other than Caco-2 cells. The most popular of these is Madin-Darby canine kidney (MDCK) cells, an epithelial cell line from the dog kidney. MDCK cells have been suggested to perform as well as Caco-2 cells in studies of passive drug permeability [56]. These cells have also been used to optimise the conditions for studies of low-solubility drugs [53]. However, as noted previously, the active transport processes of this cell line can be quite different to those of Caco-2 cells [28-30], Another cell line that only requires short-term culture is 2/4/A1, which is a conditionally immortalised rat intestinal epithelial cell line [86]. The 2/4/A1 cell line is discussed in Section 4.3.2.2 below. 

Borchardt. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability, Gastroenterology 1989, 96, 736—749... 

Hu, M. and R. Borchardt. Transport of a large neutral amino acid in a human intestinal epithelial cell line (Caco-2) uptake and efflux of phenylalanine., Biochim. Biophys. Acta 1992, 3335, 233-244... 

Tavelin, S., V. Milovic, G. Ocklind, S. Olsson, and P. Artursson. A conditionally immortalized epithelial cell line for studies of intestinal drug transport,/. Pharmacol. Exp. Ther. 1999, 290, 1212-1221... 

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]. 

The rat intestinal cell line IEC-18 has been evaluated as a model to study small intestinal epithelial permeability. This cell line forms very leaky monolayers with TER of 50 n cm2 and permeability to mannitol of 8 x 10-6 cm s 1. The IEC-18 model was proposed to be a better model than the Caco-2 monolayers for evaluating the small intestinal paracellular permeation of hydrophilic molecules. However, the leakier paracellular pathway is related to the poor differentiation level of the cells and an undeveloped paracellular barrier lacking peri-junctional actin-belt. In addition, due to the poor differentiation the cells have minute expression of transporters and are therefore not useful for studies of carrier-mediated transport [82, 84]... 

Wils, P., Warnery, A., Phung-Ba, V., Scherman, D., Differentiated intestinal epithelial cell lines as in vitro models for predicting the intestinal absorption of drugs, Cell Biol. Toxicol. 1994, 30, 393-397. 

Although infection with C. parvum is considered predominantly secretory, histopathologic studies have revealed varying degrees of villous atrophy and infiltration of inflammatory cells beneath the epithelial mucosa [85, 86], Prostaglandins, which are known to induce cAMP-mediated apical chloride secretion and inhibit electroneutral sodium chloride and water absorption in enterocytes, have been demonstrated to be elevated in a porcine model of cryptosporidiosis [87], Inflammatory cytokines such as IL-1, IL-8 and TNF-a are induced in intestinal epithelial cell lines infected with Cryptosporidium and in animal models of cryptosporidiosis and have been postulated to play a role in pathogenesis [88, 89], Expression of TNF-a and IL-1 mRNA in the majority of jejunal biopsies of adult volunteers after experimental infection were also observed, although this did not correlate with the enteric symptoms [90]. 

The permeability of the drug substance can be determined by different approaches such as pharmacokinetic studies in humans (fraction absorbed or mass balance studies) or intestinal permeability studies (in vivo intestinal perfusion studies in humans or suitable animal models or in vitro permeation studies using excised intestinal tissue or epithelial cell culture monolayers like CaCo-2 cell line). In order to avoid misclassification of a drug subject to efflux transporters such as P-glycoprotein, functional expression of such proteins should be investigated. Low- and high-permeability model... 

Thwaites DT, Hirst BH, Simmons NL (1993) Passive transepithelial absorption of thyrotropin-releasing hormone (TRH) via a paracellular route in cultured intestinal and renal epithelial cell lines. Pharm Res 10 674-681. 

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