Probiotic bacteria regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism.

Abstract

BACKGROUND:

We previously showed that the probiotic mixture, VSL#3, prevents the onset of ileitis in SAMP/YitFc (SAMP) mice, and this effect was associated with stimulation of epithelial-derived TNF. The aim of this study was to determine the mechanism(s) of VSL#3-mediated protection on epithelial barrier function and to further investigate the "paradoxical" effects of TNF in preventing SAMP ileitis.

METHODS:

Permeability was evaluated in SAMP mice prior to the onset of inflammation and during established disease by measuring transepithelial electrical resistance (TEER) on ex vivo-cultured ilea following exposure to VSL#3 conditioned media (CM), TNF or VSL#3-CM + anti-TNF. Tight junction (TJ) proteins were assessed by qRT-PCR, Western blot, and confocal microscopy, and TNFRI/TNFRII expression measured in freshly isolated intestinal epithelial cells (IEC) from SAMP and control AKR mice.

RESULTS:

Culture with either VSL#3-CM or TNF resulted in decreased ileal paracellular permeability in pre-inflamed SAMP, but not SAMP with established disease, while addition of anti-TNF abrogated these effects. Modulation of the TJ proteins, claudin-2 and occludin, occurred with a significant decrease in claudin-2 and increase in occludin following stimulation with VSL#3-CM or TNF. TNF protein levels increased in supernatants of SAMP ilea incubated with VSL#3-CM compared to vehicle, while IEC-derived TNFR mRNA expression decreased in young, and was elevated in inflamed, SAMP versus AKR mice.

CONCLUSIONS:

Our data demonstrate that the previously established efficacy of VSL#3 in preventing SAMP ileitis is due to direct innate and homeostatic effects of TNF on the gut epithelium, modulation of the TJ proteins, claudin-2 and occludin, and overall improvement of intestinal permeability.

• Authors: Daniele Corridoni, Luca Pastorelli, Benedetta Mattioli, Silviu Locovei, Dai Ishikawa, Kristen O Arseneau, Marcello Chieppa, Fabio Cominelli, Theresa T Pizarro
• Journal: PloS one (PLoS One) Vol. 7 Issue 7 Pg. e42067 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22848704 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Bacteria
• Gene Expression Regulation (drug effects)
• Homeostasis (drug effects)
• Ileitis (metabolism, microbiology, pathology, prevention & control)
• Intestinal Mucosa (drug effects, metabolism, microbiology, pathology)
• Mice
• Permeability (drug effects)
• Probiotics (pharmacology)
• Receptors, Tumor Necrosis Factor (metabolism)
• Tight Junctions (drug effects, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)