Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn's disease.
Apoptosis of active T lymphocytes constitutes a major control mechanism of immune homeostasis and tolerance. In Crohn's disease, abnormal activation of mucosal T lymphocytes against enteric bacteria is the key event triggering intestinal inflammation. Resistance of lymphocytes to apoptosis has been proposed as the pathogenetic defect. We examined the influence of bacteria-mucosa interactions on apoptosis of mucosal T lymphocytes. Ileal specimens were obtained at surgery from 12 patients with Crohn's disease. Mucosal explants from each specimen were cultured with nonpathogenic Escherichia coli ATCC 35345, Lactobacillus casei DN-114 001, or no bacteria. Cytokine release was measured in supernatant, and mononuclear cells were isolated for phenotypic characterization and Bcl-2 family protein expression. Coculture of inflamed tissue with L. casei significantly reduced the release of interleukin (IL)-6 and tumor necrosis factor alpha (P < 0.05). In addition, coculture with L. casei significantly reduced the number of T cells displaying the IL-2 receptor in the lamina propria. Expression of the antiapoptotic protein Bcl-2 in lamina propria lymphocytes was also reduced after coculture with L. casei, and the percentage of deoxyuridine triphosphate nick-end labeling positive lymphocytes increased. The nonpathogenic E. coli strain had no significant effect. In conclusion, L. casei reduces the number of activated T lymphocytes in the lamina propria of Crohn's disease mucosa. A balanced, local microecology may restore immune homeostasis.
Carol
Monica
M
Digestive System Research Unit, University Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain. mcarol@vhebron.net
Borruel
Natalia
N
Antolin
Maria
M
Llopis
Marta
M
Casellas
Francesc
F
Guarner
Francisco
F
Malagelada
Juan-R
JR
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D001419:Bacteria / Q000276:immunology*; D001973:Bromodeoxyuridine; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003424:Crohn Disease / Q000276:immunology* / Q000382:microbiology; D015536:Down-Regulation / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007780:Lacticaseibacillus casei / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013559:Symbiosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D001973:Bromodeoxyuridine