title: The Escherichia coli heat-labile enterotoxin induces apoptosis of immature lymphocytes in vivo via a glucocorticoid-dependent pathway.
abstract: Escherichia coli heat-labile enterotoxin (LT) exhibits a broad range of immunomodulatory activities, including the induction of lymphocyte-programmed cell death. However, the nature of the lymphoid populations sensitive to LT-induced apoptosis and the mechanisms used by this toxin to promote such activity are still unclear. In this study, we demonstrate that LT induces in mice a rapid increase in the levels of circulating corticosterone, resulting in a dramatic induction of cell death of immature CD4+CD8+, B220+IgM- and IgM+IgD- T and B cell progenitors, respectively. Apoptosis of these cell populations is similar to that reported after experimental treatment with corticosteroids, it is inhibited by mifepristone, a glucocorticoid receptor antagonist, and does not occur in adrenalectomized animals. These results clearly indicate that endogenous glucocorticoids are the mediators of the LT-induced cell death, which involves Bcl-2-dependent apoptotic pathways. The LT-mediated programmed cell death requires systemic exposure and the enzymatic activity of LT, since a mutant devoid of any enzymatic activity have no pro-apoptotic effect at any dose tested.
authors.affiliation: Departamento de Biología Molecular, Unidad Asociada al CIB/CSIC, Santander, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Tamayo
authors.forename: Ramón
authors.initials: R
authors.lastname: Merino
authors.forename: Jovanna
authors.initials: J
authors.lastname: González-Rojas
authors.forename: Regina
authors.initials: R
authors.lastname: Marquina
authors.forename: Inés
authors.initials: I
authors.lastname: Santiuste
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Amado
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Jesús
authors.initials: J
authors.lastname: Merino
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology; D003345:Corticosterone / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D004768:Enterotoxins / Q000235:genetics / Q000502:physiology*; D004926:Escherichia coli / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C027538:heat-labile enterotoxin, E coli; D003345:Corticosterone