A Human Colonic Cell Line Sharing Similarities With Enterocytes as a Model to Examine Oral Absorption: Advantages and Limitations of the Caco-2 Model

Delié, Florence; Rubas, Werner

doi:10.1615/critrevtherdrugcarriersyst.v14.i3.20

Cited by 377 publications

(253 citation statements)

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“…33 To study the passage of HTLV-1 across a tight epithelium, in the present study, we made use of an in vitro model in which we cocultured HTLV-1-infected lymphocytes on a monolayer of human intestinal epithelial cells grown on a Transwell filters. This model is known to reproducibly display several properties characteristic of differentiated epithelial cells, 34 and has been used for studies on virus interactions with the digestive tract. 13 To delineate an apical compartment corresponding to the tract lumen from a basolateral compartment, which corresponds to the serosal side, Caco-2 cells were grown on Transwell filter devices until differentiation and formation of tight junctions.…”

Section: Discussionmentioning

confidence: 99%

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

Martin‐Latil

Gnädig

Mallet

et al. 2012

Blood

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Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. In addition to blood transfusion and sexual transmission, HTLV-1 is transmitted mainly through prolonged breastfeeding, and such infection represents a major risk for the development of adult T-cell leukemia/lymphoma. Although HTLV-1-infected lymphocytes can be retrieved from maternal milk, the mechanisms of HTLV-1 transmission through the digestive tract remain unknown. In the present study, we assessed HTLV-1 transport across the epithelial barrier using an in vitro model. Our results show that the integrity of the epithelial barrier was maintained during coculture with HTLV-1-infected lymphocytes, because neither morphological nor functional alterations of the cell monolayer were observed. Enterocytes were not susceptible to HTLV-1 infection, but free infectious HTLV-1 virions could cross the epithelial barrier via a transcytosis mechanism.Such virions were able to infect productively human dendritic cells located beneath the epithelial barrier. Our data indicate that HTLV-1 crosses the tight epithelial barrier without disruption or infection of the epithelium to further infect target cells such as dendritic cells. The present study provides the first data pertaining to the mode of HTLV-1 transport across a tight epithelial barrier, as can occur during mother-to-child HTLV-1 transmission during breastfeeding. IntroductionApproximately 5-20 million persons worldwide are infected by the human retrovirus human T-cell leukemia virus type 1 (HTLV-1), 1 and this virus is the causative agent of severe adult T-cell leukemia/lymphoma 2 and inflammatory syndromes such as tropical spastic paraparesis/HTLV-1-associated myelopathy, a slowly progressing neurodegenerative disease that occurs in 0.5%-3% of infected persons. 3 HTLV-1 is transmitted via sexual intercourse, by transfusion with contaminated blood, and from mother to child. The latter constitutes 15%-25% of overall transmission, so it is a major method of viral spread. 4,5 Although intrauterine or perinatal transmission during birth cannot be excluded, breastfeeding is the main pathway of HTLV-1 transmission in highly endemic areas such as intertropical Africa, the Caribbean, or regions of South America. 6,7 Milk-borne transmission is supported by the presence of high levels of infected lymphocytes in maternal milk, 10 5 -10 7 of these being transferred to the child at each feed, 8,9 in addition to infected macrophages and breast epithelial cells. Furthermore, leukocytes in the breast milk remain viable after ingestion for up to 4 hours because of the buffering capacity of breast milk and the low acidity of the neonatal child's stomach. 10,11 The risk of transmission increases with the time that children are breastfed, especially when this exceeds 6 months. In addition to the duration of breastfeeding, the mother's age, Ab titers directed against HTLV-1 antigens, proviral load in the PBMCs and milk, a...

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Section: Discussionmentioning

confidence: 99%

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

Martin‐Latil

Gnädig

Mallet

et al. 2012

Blood

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“…Cultured as a monolayer, these cells can differentiate into intestinal-like absorptive cells with tight junctions and a well-differentiated brush border, which express nutrient transporters (Delie and Rubas, 1997). The apical side of these enterocyte-like cells, which contains the brush border, would be in contact with the lumen of the gut.…”

Section: Caco-2 Transepithelial Transportmentioning

confidence: 99%

“…The basal side of the cells would be in contact with the blood and lymphatic systems. As such, Caco-2 monolayers are a well-established intestinal barrier model to determine the bioavailability of substances and their transport into and out of the intestinal epithelium in vitro (Delie andRubas, 1997, Yee, 1997).…”

Section: Caco-2 Transepithelial Transportmentioning

confidence: 99%

β-Lactoglobulin-linoleate complexes: In vitro digestion and the role of protein in fatty acid uptake

Maux¹,

Brodkorb²,

Croguennec³

et al. 2013

Journal of Dairy Science

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The dairy protein β-lactoglobulin (BLG) is known to bind fatty acids such as the salt of the essential longchain fatty acid linoleic acid (cis,cis-9,12-octadecadienoic acid, n-6, 18:2). The aim of the current study was to investigate how bovine BLG-linoleate complexes, of various stoichiometry, affect the enzymatic digestion of BLG and the intracellular transport of linoleate into enterocyte-like monolayers. Duodenal and gastric digestions of the complexes indicated that BLG was hydrolyzed more rapidly when complexed with linoleate. Digested as well as undigested BLG-linoleate complexes reduced intracellular linoleate transport as compared with free linoleate. To investigate whether enteroendocrine cells perceive linoleate differently when part of a complex, the ability of linoleate to increase production or secretion of the enteroendocrine satiety hormone, cholecystokinin, was measured. Cholecystokinin mRNA levels were different when linoleate was presented to the cells alone or as part of a protein complex. In conclusion, understanding interactions between linoleate and BLG could help to formulate foods with targeted fatty acid bioaccessibility and, therefore, aid in the development of food matrices with optimal bioactive efficacy

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“…The effects of insulin on enterocytes were studied in Caco-2/TC7 cells (15,24), which enabled a separation between the effects of insulin and glucose in vitro. Differentiated Caco-2/TC7 cells segregate sucrase-isomaltase in BBM and NaKATPase in BLM (Supplemental Fig.…”

Section: Bbm Glut2 Is Decreased By Insulin In Caco-2-tc7mentioning

confidence: 99%

Insulin Internalizes GLUT2 in the Enterocytes of Healthy but Not Insulin-Resistant Mice

et al. 2008

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OBJECTIVES-A physiological adaptation to a sugar-rich meal is achieved by increased sugar uptake to match dietary load, resulting from a rapid transient translocation of the fructose/ glucose GLUT2 transporter to the brush border membrane (BBM) of enterocytes. The aim of this study was to define the contributors and physiological mechanisms controlling intestinal sugar absorption, focusing on the action of insulin and the contribution of GLUT2-mediated transport. RESEARCH DESIGN AND METHODS-The studies were performed in the human enterocytic colon carcinoma TC7 subclone (Caco-2/TC7) cells and in vivo during hyperinsulinemiceuglycemic clamp experiments in conscious mice. Chronic highfructose or high-fat diets were used to induce glucose intolerance and insulin resistance in mice. RESULTS AND CONCLUSIONS-InCaco-2/TC7 cells, insulin action diminished the transepithelial transfer of sugar and reduced BBM and basolateral membrane (BLM) GLUT2 levels, demonstrating that insulin can target sugar absorption by controlling the membrane localization of GLUT2 in enterocytes. Similarly, in hyperinsulinemic-euglycemic clamp experiments in sensitive mice, insulin abolished GLUT2 (i.e., the cytochalasin B-sensitive component of fructose absorption), decreased BBM GLUT2, and concomitantly increased intracellular GLUT2. Acute insulin treatment before sugar intake prevented the insertion of GLUT2 into the BBM. Insulin resistance in mice provoked a loss of GLUT2 trafficking, and GLUT2 levels remained permanently high in the BBM and low in the BLM. We propose that, in addition to its peripheral effects, insulin inhibits intestinal sugar absorption to prevent excessive blood glucose excursion after a sugar meal. This protective mechanism is lost in the insulin-resistant state induced by high-fat or high-fructose feeding. Diabetes 57: 555-562, 2008 I ntestinal sugar transport constantly adapts to the dietary environment. At low levels, the end products of carbohydrate digestion are absorbed by a twostep membrane-transport process involving the sodium-dependent glucose cotransporter (SGLT1) and the facilitative fructose transporter (GLUT5) in the brush border membrane (BBM) (1) lining the lumen. GLUT2 in the basolateral membrane (BLM) (2) ensures sugar exit into the blood stream (3). The level of sugar absorption is also regulated by a rapid and transient recruitment of GLUT2 into enterocyte BBM (4,5). A high sugar intake is a physiological regulator of this process, increasing monosaccharide uptake threefold in vivo (6). The recruitment of GLUT2 in BBM was also observed in conditions of increased calorie demand and glucagon-like peptide 2 treatment (7-11).The mechanisms by which GLUT2 leaves the BBM in the absence of luminal sugar (interprandial periods) are unknown. Of the possible physiological stimuli occurring during feeding, insulin was thought to be a candidate because it exerts systemic hypoglycemic effects by stimulating the translocation of GLUT4 into the plasma membrane of skeletal muscle and adipose cells (rev. in 12) and d...

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A Human Colonic Cell Line Sharing Similarities With Enterocytes as a Model to Examine Oral Absorption: Advantages and Limitations of the Caco-2 Model

Cited by 377 publications

References 0 publications

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

β-Lactoglobulin-linoleate complexes: In vitro digestion and the role of protein in fatty acid uptake

Insulin Internalizes GLUT2 in the Enterocytes of Healthy but Not Insulin-Resistant Mice

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