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

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

doi:10.1042/bcj20160390

Cited by 21 publications

(18 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…227,228 Recent studies have shown that the pro-inflammatory cytokines interferon (IFN)g and TNFa increase CgA þ eecs in an autophagy and protein kinase B (Akt) dependent manner. 229 Bromodeoxyuridine (BrdU) pulse-chase labeling of proliferative cells has demonstrated that increases in 5-HT þ cells during TNBS-colitis are due to alterations in the stem-cell niche rather than division of existing eecs. 230 Collectively this points to cytokine mediated alterations of specific eec subsets via adaptation at the stem-cell niche as opposed to proliferation of existing eecs.…”

Section: Mechanistic Cross-talk Between Enteroendocrine Cells and Immmentioning

confidence: 99%

Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity

2018

View full text Add to dashboard Cite

The intestinal epithelium must balance efficient absorption of nutrients with partitioning commensals and pathogens from the bodies' largest immune system. If this crucial barrier fails, inappropriate immune responses can result in inflammatory bowel disease or chronic infection. Enteroendocrine cells represent 1% of this epithelium and have classically been studied for their detection of nutrients and release of peptide hormones to mediate digestion. Intriguingly, enteroendocrine cells are the key sensors of microbial metabolites, can release cytokines in response to pathogen associated molecules and peptide hormone receptors are expressed on numerous intestinal immune cells; thus enteroendocrine cells are uniquely equipped to be crucial and novel orchestrators of intestinal inflammation. In this review, we introduce enteroendocrine chemosensory roles, summarize studies correlating enteroendocrine perturbations with intestinal inflammation and describe the mechanistic interactions by which enteroendocrine and mucosal immune cells interact during disease; highlighting this immunoendocrine axis as a key aspect of innate immunity.

show abstract

Section: Mechanistic Cross-talk Between Enteroendocrine Cells and Immmentioning

confidence: 99%

Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity

2018

View full text Add to dashboard Cite

show abstract

“…The CgA cell density is increased in patients with IBD, and in animal models of human UC and CD, with the exception of trinitrobenzene sulfonic acid (TNBS)-induced colitis[ 9 , 117 , 244 - 248 ] (Figure 3 ). The administration of the proinflammatory cytokines INFγ and TNFα and the induction of colitis by dextran sodium sulfate (DSS) in mice were found to increase the number of CgA cells[ 249 ].…”

Section: Nes Nepa In Ibdmentioning

confidence: 99%

Gastrointestinal neuroendocrine peptides/amines in inflammatory bowel disease

El‐Salhy

Tefera

Hausken

et al. 2017

WJG

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic recurrent condition whose etiology is unknown, and it includes ulcerative colitis, Crohn’s disease, and microscopic colitis. These three diseases differ in clinical manifestations, courses, and prognoses. IBD reduces the patients’ quality of life and is an economic burden to both the patients and society. Interactions between the gastrointestinal (GI) neuroendocrine peptides/amines (NEPA) and the immune system are believed to play an important role in the pathophysiology of IBD. Moreover, the interaction between GI NEPA and intestinal microbiota appears to play also a pivotal role in the pathophysiology of IBD. This review summarizes the available data on GI NEPA in IBD, and speculates on their possible role in the pathophysiology and the potential use of this information when developing treatments. GI NEPA serotonin, the neuropeptide Y family, and substance P are proinflammatory, while the chromogranin/secretogranin family, vasoactive intestinal peptide, somatostatin, and ghrelin are anti-inflammatory. Several innate and adaptive immune cells express these NEPA and/or have receptors to them. The GI NEPA are affected in patients with IBD and in animal models of human IBD. The GI NEPA are potentially useful for the diagnosis and follow-up of the activity of IBD, and are candidate targets for treatments of this disease.

show abstract

“…IFNγ activates PI3K/Akt signaling in the mucosa of colitic mice and reduces proliferation [2] , [3] , [14] , [16] , therefore we analyzed mTORC1 status in SW480 and RKO cells treated with IFNγ for 3 h. As shown in Figure 2 A increased phosphorylation of STAT1 phosphorylation at Y701 was observed after IFNγ stimulation demonstrating the functionality of our assay. Furthermore, phosphorylation of Akt at ser473, β-catenin at ser552, mTOR at ser2448 and P70S6K at Thr389 was induced after cytokine treatment.…”

Section: Resultsmentioning

confidence: 71%

“…Rapamycin used as previously reported by us [14] Doxorubicin was obtained from Pfizer and used at 3.45 μM. AZD8055 and XAV939 were used as previously reported by us [16] , [17] . Dextran sulfate sodium YD318041799 (Carbosynth, San Diego, CA) was dissolved at 3% in drinking water.…”

Section: Methodsmentioning

confidence: 99%

mTORC1 Prevents Epithelial Damage During Inflammation and Inhibits Colitis-Associated Colorectal Cancer Development

Gutiérrez-Martínez

Rubio

Piedra-Quintero

et al. 2019

Translational Oncology

View full text Add to dashboard Cite

Epithelial cells lining the intestinal mucosa constitute a selective-semipermeable barrier acting as first line of defense in the organism. The number of those cells remains constant during physiological conditions, but disruption of epithelial cell homeostasis has been observed in several pathologies. During colitis, epithelial cell proliferation decreases and cell death augments. The mechanism responsible for these changes remains unknown. Here, we show that the pro-inflammatory cytokine IFNγ contributes to the inhibition of epithelial cell proliferation in intestinal epithelial cells (IECs) by inducing the activation of mTORC1. Activation of mTORC1 in response to IFNγ was detected in IECs present along the crypt axis and in colonic macrophages. mTORC1 inhibition enhances cell proliferation, increases DNA damage in IEC. In macrophages, mTORC1 inhibition strongly reduces the expression of pro-inflammatory markers. As a consequence, mTORC1 inhibition exacerbated disease activity, increased mucosal damage, enhanced ulceration, augmented cell infiltration, decreased survival and stimulated tumor formation in a model of colorectal cancer CRC associated to colitis. Thus, our findings suggest that mTORC1 signaling downstream of IFNγ prevents epithelial DNA damage and cancer development during colitis.

show abstract

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

Cited by 21 publications

References 60 publications

Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity

Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity

Gastrointestinal neuroendocrine peptides/amines in inflammatory bowel disease

mTORC1 Prevents Epithelial Damage During Inflammation and Inhibits Colitis-Associated Colorectal Cancer Development

Contact Info

Product

Resources

About