title: The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium.
abstract: The gastrointestinal tract is the largest hormone-producing organ in the body due to a specialized cell population called enteroendocrine cells (EECs). The number of EECs increases in the mucosa of inflammatory bowel disease patients; however, the mechanisms responsible for these changes remain unknown. Here, we show that the pro-inflammatory cytokines interferon γ (IFNγ) and tumor necrosis factor α (TNFα) or dextran sulfate sodium (DSS)-induced colitis increase the number of EECs producing chromogranin A (CgA) in the colonic mucosa of C57BL/6J mice. CgA-positive cells were non-proliferating cells enriched with inactive phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and autophagy markers. Moreover, inhibition of Akt and autophagy prevented the increase in CgA-positive cells after IFNγ/TNFα treatment. Similarly, we observed that CgA-positive cells in the colonic mucosa of patients with colitis expressed Akt and autophagy markers. These findings suggest that Akt signaling and autophagy control differentiation of the intestinal EEC lineage during inflammation.
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Cinvestav Zacatenco, Av. Instituto Politécnico Nacional #2508, Col. San Pedro Zacatenco, 07360 Mexico City, Mexico.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Hernández-Trejo
authors.affiliation: Department of Morphology, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, 11340 Mexico City, Mexico.
authors.forename: Dimelza
authors.initials: D
authors.lastname: Suárez-Pérez
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Cinvestav Zacatenco, Av. Instituto Politécnico Nacional #2508, Col. San Pedro Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Itzel Zenidel
authors.initials: IZ
authors.lastname: Gutiérrez-Martínez
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Cinvestav Zacatenco, Av. Instituto Politécnico Nacional #2508, Col. San Pedro Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Omar Eduardo
authors.initials: OE
authors.lastname: Fernandez-Vargas
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Cinvestav Zacatenco, Av. Instituto Politécnico Nacional #2508, Col. San Pedro Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Carolina
authors.initials: C
authors.lastname: Serrano
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Cinvestav Zacatenco, Av. Instituto Politécnico Nacional #2508, Col. San Pedro Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Aurora Antonia
authors.initials: AA
authors.lastname: Candelario-Martínez
authors.affiliation: Department of Molecular Biomedicine, Cinvestav Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Meraz-Ríos
authors.affiliation: Department of Molecular Biomedicine, Cinvestav Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Alí Francisco
authors.initials: AF
authors.lastname: Citalán-Madrid
authors.affiliation: Department of Molecular Biomedicine, Cinvestav Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Marcela
authors.initials: M
authors.lastname: Hernández-Ruíz
authors.affiliation: Department of Morphology, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, 11340 Mexico City, Mexico.
authors.forename: Elba
authors.initials: E
authors.lastname: Reyes-Maldonado
authors.affiliation: Research Division, School of Medicine, Universidad Nacional Autónoma de México, 04510 Mexico City, Mexico Immunology and Proteomics Laboratory, Hospital Infantil de México Federico Gómez, Dr. Márquez #162, Col. Doctores, 06720 Mexico City, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Valle-Rios
authors.affiliation: General Hospital l Ticomán, 07330 Mexico City, Mexico.
authors.forename: Jacobo H
authors.initials: JH
authors.lastname: Feintuch-Unger
authors.affiliation: Department of Molecular Biomedicine, Cinvestav Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Michael
authors.initials: M
authors.lastname: Schnoor
authors.affiliation: Department of Molecular Biomedicine, Cinvestav Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Villegas-Sepúlveda
authors.affiliation: Immunology and Proteomics Laboratory, Hospital Infantil de México Federico Gómez, Dr. Márquez #162, Col. Doctores, 06720 Mexico City, Mexico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Medina-Contreras
authors.affiliation: Department of Physiology, Biophysics and Neurosciences, Cinvestav Zacatenco, Av. Instituto Politécnico Nacional #2508, Col. San Pedro Zacatenco, 07360 Mexico City, Mexico.
authors.forename: Porfirio
authors.initials: P
authors.lastname: Nava
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D018938:Caco-2 Cells; D053379:Chromogranin A / Q000378:metabolism*; D003092:Colitis / Q000378:metabolism; D003106:Colon / Q000166:cytology*; D016207:Cytokines / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055099:Neuroendocrine Cells / Q000187:drug effects* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D053379:Chromogranin A; D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D051057:Proto-Oncogene Proteins c-akt
keywords: 14-3-3 proteins; Akt; Chromogranin A; autophagy; colitis; differentiation