The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium

Antonio José Hernández-Trejo, Dimelza Suárez-Pérez, Zenidel Itzel Gutiérrez-Martínez, Eduardo Omar Fernandez-Vargas, Antonia Aurora Candelario-Martínez, Marco Antonio Meraz-Ríos, Alí Francisco Citalán-Madrid, Marcela Hernández-Ruíz, Elba Reyes-Maldonado, Ricardo Valle-Rios, Jacobo H. Feintuch-Unger, Nicolás Villegas-Sepúlveda, Oscar Medina-Contreras, Carolina Serrano, Schnoor Michael, Porfirio Nava

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13 Scopus citations

Abstract

© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society. 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.
Original languageAmerican English
Pages (from-to)3805-3818
Number of pages3423
JournalBiochemical Journal
DOIs
StatePublished - 1 Jan 2016

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    Hernández-Trejo, A. J., Suárez-Pérez, D., Gutiérrez-Martínez, Z. I., Fernandez-Vargas, E. O., Candelario-Martínez, A. A., Meraz-Ríos, M. A., Citalán-Madrid, A. F., Hernández-Ruíz, M., Reyes-Maldonado, E., Valle-Rios, R., Feintuch-Unger, J. H., Villegas-Sepúlveda, N., Medina-Contreras, O., Serrano, C., Michael, S., & Nava, P. (2016). The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium. Biochemical Journal, 3805-3818. https://doi.org/10.1042/BCJ20160390