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© 2003 The American Society for Nutritional Sciences J. Nutr. 133:2176-2179, July 2003

Biochemical and Molecular Actions of Nutrients

Glutamine and Barrier Function in Cultured Caco-2 Epithelial Cell Monolayers

Vincent G. DeMarco, Nan Li, Justin Thomas, Christopher M. West* and Josef Neu3

Department of Pediatrics and * Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610

3To whom correspondence should be addressed. E-mail: neuj{at}peds.ufl.edu.


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
Dietary glutamine (Gln) has been shown to be important for maintenance of the intestinal barrier. To investigate the role of the epithelium in this Gln dependence, Caco-2 cells were raised on semipermeable membranes under conditions that model different regions of the crypt and villus. Gln availability was controlled by addition to the medium and treatment with methionine sulfoximine to inhibit Gln synthetase (GS). Barrier function was assayed by measuring transepithelial electrical resistance and fluxes of [14C]mannitol and fluoroscein isothiocyanate–dextran. The barrier function of these monolayers was found to require the Gln provided either in the medium at the apical or basal surface or via GS. However, the barrier was no more sensitive to Gln deprivation than it was to accumulation or maintenance of total protein. These results suggest that the in vivo dependence of the gut mucosal barrier on Gln likely involves roles separate from maintenance of the epithelial barrier per se.

KEY WORDS: • intestine • nutrition • cell culture • butyrate

The intestinal lining separates the luminal and mucosal compartments and constitutes a critical barrier to antigens and infectious agents. Disruption of the tight junctions that modulate the paracellular pathway between adjacent epithelial cells (1) results in a leaky gut. Evidence suggests that supplemental glutamine (Gln) helps to maintain intestinal mucosal integrity, especially during stress, and blunts increased gut permeability associated with experimental sepsis (2). This may involve the epithelium itself, because Gln starvation of monolayers of Caco-2 cells, derived from a human colon adenocarcinoma and frequently used to model the intestinal epithelium (3), leads to increased bacterial translocation (4). This effect is more pronounced when Gln is deprived from the apical surface of the cells, suggesting that enteral may be more important than parenteral Gln supplementation in vivo. The mechanism by which Gln contributes to the mucosal barrier function might involve the paracellular pathway (2).

Caco-2 cells grow to confluence and spontaneously differentiate in a process requiring 21 d (5). At that time cells exhibit several classic differentiation markers typically found in mature differentiated intestinal epithelial cells, such as the appearance of microvilli and the expression of alkaline phosphatase (ALP) and sucrase-isomaltase. The differentiated Caco-2 cell monolayer exhibits a phenotype that mimics the crypt neck and villus base (5). More rapid differentiation of this same cell line can be induced by exposure to n-butyrate (BT) for 2 d, and BT-induced Caco-2 cells express characteristic markers of villus tip cells, such as components of the urokinase system (5). The fact that spontaneous and BT-induced differentiated Caco-2 cells exhibit different phenotypes characteristic of villus tip cells or crypt base cells affords an opportunity to examine junctional integrity at different points along the crypt-to-villus axis. The rationale for this approach is also related to recent evidence suggesting that differences in the paracellular permeability of enterocytes along the crypt-villus axis may be related to the differential localization of transmembrane junctional proteins in the claudin family (6). Paracellular permeability of enterocytes may vary along the crypt-villus axis (5).

The paracellular pathway of Caco-2 monolayers can be sensitively monitored by serial measurements of transepithelial resistance (TER) in a bicameral system, or by using permeability markers such as [14C]mannitol and fluorescent dextrans (5–9).


   MATERIALS AND METHODS
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 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 LITERATURE CITED
 
Cell culture.

Caco-2 cells (passage 20–30; American Type Culture Collection, Manassas, VA) were seeded into 24-well Biocoat cell culture inserts (coated with type I rat-tail collagen; BD Labware, Bedford, MA) at 200,000 cells/well as previously described (10). The upper and lower chambers contained 0.5 and 1.0 mL of medium that, for the spontaneously differentiating 21-d cultures, consisted of 20% fetal bovine serum, antibiotics and 4 mmol/L Gln prepared in Gln-free minimum essential medium (Life Technologies; Grand Island, NY). The medium was changed every other day. After 21 d, cultures were fed with Gln-free DMEM supplemented with Mito+ serum extender (BD Biosciences, Mountain View, CA), a proprietary serum substitute, with Gln, Glu, NH3 or L-S-(3-amino-3-carboxypropyl)-S-methylsulfoximine (MSO) added as indicated.

For short-term cultures, Caco-2 cells were fed daily with DMEM containing 4 mmol/L Gln and Mito+ serum extender. On d 2, Gln-free DMEM was supplemented with 4 mmol/L BT (10), and Gln and MSO were adjusted as described.

Enzyme assays.

Caco-2 cells were scraped and sonicated in 0.5% Nonidet P-40 in PBS. ALP activity was determined using an alkaline phosphatase kit from Sigma-Aldrich (St. Louis, MO). Protein and Gln synthetase (GS) were measured as previously described (11).

Monolayer resistance.

Electrical resistance across the monolayer was measured before the medium change as previously described (11).

Transepithelial mannitol and dextran permeability.

D-[1-14C-mannitol] (2.15 GBq/mmol) or fluoroscein isothiocyanate (FITC)-dextran (Mr, 4000) were added at 0.2 mCi/L or 200 mg/L to the upper chamber without medium change. Aliquots were withdrawn from the upper and lower chambers after 2 h and assayed for radioactivity by scintillation counting or for fluorescence at 515 nm with excitation at 492 nm. An apparent permeability coefficient (Papp) was calculated by the following formula: Papp (cm/s) = P/(A x Co), where P is the permeability rate (mol/s), Co is the initial concentration in the upper chamber (mol/ml), and A is the surface area of the monolayer (12).

Statistical analysis.

Two-way ANOVA was performed to determine whether Gln and MSO affected the outcomes. Pairwise multiple comparisons were done using the Bonferroni t test. Analyses were performed using SigmaStat software (SPSS Science, Chicago, IL) and differences were considered significant at P < 0.05.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 LITERATURE CITED
 
Three-week differentiated Caco-2 cultures.

Time course analyses (data not shown) showed that by 21 d, these cultures achieved maximal levels of protein, the differentiation marker ALP and TER, as previously described (9,11). After an additional 5 d, the mean TER values of cultures maintained in 0.2–4 mmol/L Gln did not differ and ranged from 137 to 213 {Omega} · cm2 (Fig. 1A). At 0 mmol/L Gln, TER values were lower (112 {Omega} · cm2) and varied considerably among cultures. During this 5-d interval, total cellular protein did not differ among cultures with Gln levels ≥ 0.6 mmol/L, the physiological level in serum (data not shown). In contrast, total protein was 26 and 40% lower at 0.2 and 0 mmol/L Gln, respectively. However, ALP specific activity did not differ among cultures (data not shown), indicating that the differentiation status of the cells was not affected at limiting Gln.



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  		FIGURE 1 Dependence of TER and permeability in 3-wk Caco-2 cultures on glutamine (Gln). Monolayers (21 d) were incubated in the presence of Gln and/or L-S-(3-amino-3-carboxypropyl)-S-methylsulfoximine (MSO) as indicated. On d 26, transepithelial resistance (TER) (A), fluoroscein isothiocyanate–dextran permeability (B) and [14C]mannitol permeability (C) were measured. Values are means ± SD; n = 3–4 independent samples. *P < 0.05, **P < 0.01, vs. 0.6 mmol/L Gln. Papp, apparent permeability coefficient.

 
Gln is also provided by the action of GS in Caco-2 cells (11), which might explain why some cultures were able to sustain normal TER values in the absence of added Gln. To test this possibility, cultures were incubated in the presence of 1 mmol/L MSO, which causes >95% inhibition of GS assayed in extracts from treated cells (11). Cultures incubated with no Gln and MSO had diminished TER (<30% of the normal value), and variability was reduced greatly (Fig. 1A). Time course analysis showed that loss of TER began after 3 d of treatment (data not shown). The effect of MSO appeared to be specific for GS, because the TER reduction was rescued by the inclusion of 0.2 mmol/L Gln. Therefore, 0.2 mmol/L Gln is sufficient for normal TER values in the absence of Gln supplied by GS, but GS alone is unable to provide enough Gln to consistently maintain normal TER. Although ALP levels were normal in these 0-Gln and -MSO cultures, protein content was decreased 50% from its initial level at 21 d, showing that under these conditions Gln starvation also had a major impact on cell sustainability (data not shown).

To determine whether the decline in TER reflected increased paracellular permeability, the upper chambers of a parallel set of 26-d cultures were supplemented with FITC-dextran or [14C]mannitol. After 2 h, aliquots from the lower chamber were analyzed for fluorescence or radioactivity. Only low levels of tracer were found in the lower chamber of cultures containing ≥0.2 mmol/L Gln, even in the presence of MSO (Fig. 1B and C). With no Gln, a slight (P > 0.1) increase in Papp value was seen using FITC-dextran (Fig. 1B), but a substantial increase was seen using the mannitol tracer (Fig. 1C). In the presence of MSO, high levels of permeability for both tracers were observed in the 0-Gln cultures. Therefore, the permeability results corroborated the TER data in showing increased leakiness in 0-Gln cultures in the presence of MSO and an intermediate effect in 0-Gln cultures in the absence of MSO.

To address whether the decline in TER observed in the Gln-deprived cultures was reversible, 0.6 mmol/L Gln was restored to the cultures for five additional days (d 26–31). TER values were nearly normal for the Gln-rescued cultures regardless of whether MSO was present (Fig. 2). In contrast, TER values declined further in cultures that remained on 0 Gln. Addition of 0.6 mmol/L Glu and 50 µmol/L ammonium acetate, substrates for GS, partially reversed the effect of prior treatment with 0 Gln, but only in the absence of the GS inhibitor MSO. Thus, the effects of Gln deprivation did not involve irreversible cell damage.



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  		FIGURE 2 Caco-2 cell recovery from glutamine (Gln) deprivation. Cultures were reared from d 21 to 26 as in Figure 1 and then continued in the presence or absence of or L-S-(3-amino-3-carboxypropyl)-S-methylsulfoximine (MSO) as described. Gln and glutamate (Glu) concentrations are given in mmol/L. Cultures receiving Glu were also given 50 µmol/L ammonium acetate. Transepithelial resistance values (mean ± SD) were obtained on d 31 and are reported as the percentage of change from the d 26 value, with 100% meaning no change. *Change from d 26 to 31, P < 0.05.

 
Short-term high density BT-treated cultures.

This alternative culture model mimics a region higher in the villus (see Introduction). Cultures were seeded at high density and after 2 d were treated with serum-free medium containing 4 mmol/L BT and 0.6 mmol/L Gln. After two more days, their ALP levels increased to ≥500 nmol · min-1 mg · protein-1, fourfold higher than that of 21-d cultures. TER values were 6–10 times higher (~1000 {Omega} · cm2) (Fig. 3A), and protein content was about the same (40 µg/well), as found previously (5).



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  		FIGURE 3 Effect of butyrate (BT) treatment on TER and permeability in Caco-2 cells. Monolayers were induced with BT on d 2, and glutamine (Gln) [or glutamate (Glu)] and L-S-(3-amino-3-carboxypropyl)-S-methylsulfoximine (MSO) levels were adjusted as indicated. Transepithelial resistance (TER) (A) and permeability to dextran (B) and mannitol (C) were measured on d 4. Values are means ± SD; n = 3–4 independent samples. (A) *P < 0.05, **P < 0.01; (B, C) **P < 0.01, vs. 0.6 mmol/L Gln. Papp, apparent permeability coefficient.

 
In cultures containing 0–0.2 mmol/L Gln, variable effects ranging from no increase in TER to the normal increase seen in 0.6 mmol/L Gln cultures were observed, resulting in a high SD (Fig. 3A). No increase in permeability to FITC-dextran was detected, but a slight increase in permeability to [14C] mannitol was observed (P > 0.05, Fig. 3B and C). However, the 0-Gln cultures contained only ~40% of the total protein of 0.6 mmol/L Gln cultures, consistent with the findings in rat intestinal IEC-6 cells (13) and only ~60% of the level of ALP (data not shown). Therefore, TER was no more sensitive to Gln deprivation than to accumulation of total protein and induction of ALP under these conditions.

The variable effects of Gln starvation suggested that, as for the 21-d cultures, Gln might be provided from an alternative source, such as GS or protein turnover, which could marginally support the TER increase. BT-treated cell extracts possessed GS activity of 2.2 mmol · h-1 µg protein-1, similar to that of spontaneously differentiated Caco-2 cells (11). The potential importance of GS was tested first by determining whether the GS substrates (0.6 mmol/L Glu and 50 µmol/L ammonium acetate) could replace Gln. This substitution yielded a consistent near-normal increase in TER (Fig. 3A), protein content and ALP (not shown), suggesting an active role for GS. As a second approach, GS was inhibited by adding MSO as above (Fig. 3A). The MSO-treated cultures lacking Gln had very low protein content (15 µg/well) and reduced ALP (<50 nmol · min-1 mg · protein-1). TER did not increase from the initial mean of 150 {Omega} · m2 (Fig. 3A), and fluxes of FITC-dextran and [14C]mannitol increased dramatically (Fig. 3B and C). This effect was reversible because the mean TER almost doubled when cultures were continued for an additional day after adding 0.6 mmol/L Gln (not shown). Addition of MSO in the presence of 0.2 or 0.6 mmol/L Gln did not affect the increases in TER (Fig. 3A) and ALP activity in the absence of MSO. Glu (0.6 mmol/L) and 50 µmol/L ammonium acetate did not substitute for 0.6 mmol/L Gln in the presence of MSO. Together these results indicate that the inhibitory effects of MSO on TER at lower Gln concentrations were specific to the inhibition of GS and argue that cultures containing no added Gln utilize endogenously produced Gln to support their barrier function.

Apical compared with basal presentation of Gln.

There is some evidence that the barrier function of Caco-2 monolayers is selectively supported by Gln supplied at the apical surface (see Introduction). The high TER levels of d 2 monolayers suggested that Gln provided to either the upper or lower chamber might be kinetically confined to that chamber long enough to test whether Gln is required on one or both sides to support the rapid increase in TER induced by BT. MSO-treated cultures presented 0.6 mmol/L Gln in both chambers exhibited the expected rapid rise in TER on d 3, which leveled off by d 4, whereas cultures not given Gln exhibited only a slight increase in TER (Fig. 4). Cultures provided 0.6 mmol/L Gln in only the apical or basal chamber showed the normal two to three times increase observed when Gln was provided on both sides. Therefore, Caco-2 monolayers were able to take up Gln from either their basal or apical surface to support rapid increases in TER in response to BT.



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  		FIGURE 4 Effect of polarized glutamine (Gln) presentation on Caco-2 cells. Cultures raised as described in Figure 3 were treated on d 2 with butyrate and L-S-(3-amino-3-carboxypropyl)-S-methylsulfoximine, and Gln, which was added to the upper and lower chambers as indicated. Values are means ± SD; n = 3–4 independent samples. Significance relative to d 2 values with the same treatment, *P < 0.05; **P < 0.01. Significance relative to 0 Gln, same day, #P < 0.05; ##P < 0.01. TER, transepithelial resistance.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
LITERATURE CITED
 
In this study, we found that a low level of Gln (0.2 mmol/L), below the mean plasma concentration (0.6 mmol/L), was sufficient to support epithelial barrier function based on TER measurements and permeability to [14C]mannitol (Mr, 184) and FITC-dextran (Mr, 4000). However, complete nutritional deprivation of Gln had a variable effect as defined by TER. TER is a highly sensitive measure of the barrier that is not necessarily physiologically meaningful (5–9). The variable increased permeability, seen also in some trials to mannitol but not dextran, suggests that the TER increase might be physiologically important and selective for small molecules. The effect was observed in both cell culture models, the spontaneously differentiated 21-d cultures modeling the crypt neck and villus base, and the 4-d BT-induced cultures modeling the villus tip cells. However, small reductions were also observed in total protein level and, for the BT-induced cultures, ALP levels. This suggests that the barrier deficit may be due to global effects on epithelial cell function. Consistent with this concept, some cultures exhibited no barrier deficit in the absence of added Gln, altogether indicating that maintenance of the barrier is a robust feature of the epithelium.

In the absence of added Gln, sufficient Gln may be provided de novo by GS. GS was active in extracts of Caco-2 cells (see above; Ref. 11), and addition of the precursor substrates Glu and ammonium acetate consistently rescued TER in Gln-deprived cells, if GS was not inhibited by MSO. When endogenous GS was inhibited by MSO in addition to nutritional deprivation of Gln, both culture systems exhibited dramatic breakdown in barrier function. The barrier function breakdown was reversible, suggesting that it is not the result of permanent cell damage. The barrier deficit was associated with a low overall protein level, indicating that the effect on permeability may be indirect. These studies establish a role for Gln, either from the medium or via endogenous synthesis, in supporting epithelial cell protein levels and the barrier function of the monolayer.

Our findings indicated that Gln provided at either the apical or basal surface rescued TER as well as Gln provided in both. This is consistent with evidence for apical-Gln transport pathways in Caco-2 cells (14) and basolateral transport of Gln in the intestinal epithelium (15).

Gln supplementation has been demonstrated to improve intestinal-barrier function in highly stressed patients (16) and in animal models of endotoxin-induced permeability (2) and parenteral nutrition (17). The implication is that luminal microorganisms and toxins can translocate to the subepithelium (i.e., a leaky gut). The current study suggests that, under nonpathologic conditions, Gln deprivation does not compromise barrier function until the epithelium is affected constitutionally as evidenced by an inability to sustain protein content. Sufficient Gln may be provided either via synthesis if Glu and NH3 are available or from low levels presented at the apical or basal epithelial surface. So how does nutritional Gln mitigate against a leaky gut? If supplemental Gln does more than support constitutional cell health, it may counteract some other stressor not modeled in this study; e.g., bacteria may produce factors that target GS activity or N availability, or affect tight junctions directly. Alternatively, Gln may support specialized functions for other epithelial cell types not examined in this study. Additional understanding of the roles of Gln and GS will probably require study of the epithelium in the context of pathologic and nutritional factors in the environment of an active submucosa as found in vivo.


   FOOTNOTES
 
1 Supported by National Institutes of Health Grant RO1HD38954 to J.N. Back

2 Present address: Department of Child Health, Division of Cardiology, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO 65212. Back

4 Abbreviations used: ALP, alkaline phosphatase; BT, n-butyrate; FITC, fluoroscein isothiocyanate; Gln, L-glutamine; Glu, L-glutamate; GS, Gln synthetase; MSO, L-S-(3-amino-3-carboxypropyl)-S-methylsulfoximine; TER, transepithelial resistance. Back

Manuscript received 14 November 2002. Initial review completed 11 December 2002. Revision accepted 24 March 2003.


   LITERATURE CITED
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 

1. Nusrat, A., Turner, J. R. & Madara, J. L. (2000) Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am. J. Physiol. Gastrointest. Liver Physiol. 279:G851-G857.[Abstract/Free Full Text]

2. Dugan, M. E. & McBurney, M. I. (1995) Luminal glutamine perfusion alters endotoxin-related changes in ileal permeability of the piglet. J. Parenter. Enteral Nutr. 19:83-87.[Abstract/Free Full Text]

3. Pinto, M., Robine-Leon, S., Appay, M. D., Kerdinger, M., Triadon, N., Dussaclx, E., Lacroix, B., Simon-Assmann, P., Haffen, K., Fogh, J. & Zweibaum, A. (1983) Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture. Biol. Cell 47:323-330.

4. Panigrahi, P., Gewolb, I. H., Bamford, P. & Horvath, K. (1997) Role of glutamine in bacterial transcytosis and epithelial cell injury. J. Parenter. Enteral Nutr. 21:75-80.[Abstract/Free Full Text]

5. Mariadason, J. M., Rickard, K. L., Barkla, D. H., Augenlicht, L. H. & Gibson, P. R. (2000) Divergent phenotypic patterns and commitment to apoptosis of Caco-2 cells during spontaneous and butyrate-induced differentiation. J. Cell. Physiol. 183:347-354.[Medline]

6. Rahner, C., Mitic, L. L. & Anderson, J. M. (2001) Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut. Gastroenterology 120:411-422.[Medline]

7. Cruz, N., Qi, L., Alvarez, X., Berg, R. D. & Deitch, E. A. (1994) The Caco-2 cell monolayer system as an in vitro model for studying bacterial-enterocyte interactions and bacterial translocation. J. Burn Care Rehabil. 15:207-212.[Medline]

8. Madara, J. L. (1998) Regulation of the movement of solutes across tight junctions. Annu. Rev. Physiol. 60:143-159.[Medline]

9. Mariadason, J. M., Barkla, D. H. & Gibson, P. R. (1997) Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model. Am. J. Physiol. 272:G705-G712.

10. Chong, S., Dando, S. A. & Morrison, R. A. (1997) Evaluation of Biocoat intestinal epithelium differentiation environment (3-day cultured Caco-2 cells) as an absorption screening model with improved productivity. Pharm. Res. 14:1835-1837.[Medline]

11. Weiss, M. D., DeMarco, V., Strauss, D. M., Samuelson, D. A., Lane, M. E. & Neu, J. (1999) Glutamine synthetase: a key enzyme for intestinal epithelial differentiation?. J. Parenter. Enteral Nutr. 23:140-146.[Abstract/Free Full Text]

12. Biganzoli, E., Cavenaghi, L. A., Rossi, R., Brunati, M. C. & Nolli, M. L. (1999) Use of a Caco-2 cell culture model for the characterization of intestinal absorption of antibiotics. Farmaco 54:594-599.[Medline]

13. DeMarco, V., Dyess, K., Strauss, D., West, C. M. & Neu, J. (1999) Inhibition of glutamine synthetase decreases proliferation of cultured rat intestinal epithelial cells. J. Nutr. 129:57-62.[Abstract/Free Full Text]

14. Souba, W. W., Pan, M. & Stevens, B. R. (1992) Kinetics of the sodium-dependent glutamine transporter in human intestinal cell confluent monolayers. Biochem. Biophys. Res. Commun. 188:746-753.[Medline]

15. Taylor, P. M., Egan, C. J. & Rennie, M. J. (1989) Transport of glutamine across blood-facing membranes of perfused rat jejunum. Am. J. Physiol. 256:E550-E558.[Medline]

16. Neu, J., DeMarco, V. G. & Li, N. (2002) Glutamine: clinical applications and mechanisms of action. Curr. Opin. Clin. Nutr. Metab. Care 5:69-75.[Medline]

17. Li, J., Langkamp-Henken, B., Suzuki, K. & Stahlgren, L. H. (1994) Glutamine prevents parenteral nutrition induced increases in intestinal permeability. J. Parenter. Enteral Nutr. 18:303-307.[Abstract/Free Full Text]




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