Lack of enteral nutrition—effects on the intestinal immune system

Wildhaber, Barbara E.; Yang, Hua; Spencer, Ariel U.; Drongowski, Robert A.; Teitelbaum, Daniel H.

doi:10.1016/j.jss.2004.06.015

Cited by 114 publications

(106 citation statements)

References 33 publications

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“…Figure 8 shows that fasting induced iNOS mRNA, which was suppressed by AG. Because of intimate anatomical localization of IEL located at basolateral surfaces of intestinal epithelial cells (IEC), possibly implicating a functional dialogue between the two cells, recent reports indicated phenotypic changes of IEC during administration of total parenteral nutrition via IEL-derived cytokines such as IFN-␥ (52,55,56). We therefore investigated the effects of fasting and AG treatment on transcriptional expression of IFN-␥.…”

Section: Body Weight Changesmentioning

confidence: 99%

Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

Ito

Uchida

Yokote

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ito J, Uchida H, Yokote T, Ohtake K, Kobayashi J. Fastinginduced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-␥ in rat. Am J Physiol Gastrointest Liver Physiol 298: G916 -G926, 2010. First published April 8, 2010 doi:10.1152/ajpgi.00429.2009 is associated with intestinal apoptosis in health and disease. This study aimed to investigate the role of intestinal NO in the regulation of apoptosis during fasting in rats. Male Wistar rats were divided into two groups and subcutaneously injected with saline (SA) or aminoguanidine (AG), followed by fasting for 24, 48, 60, and 72 h. At each time point, the jejunum was subjected to histological evaluation for enterocyte apoptosis by histomorphometric assessment and TUNEL analysis. We performed immunohistochemistry for inducible NO synthase (iNOS) expression in the jejunum and measured tissue nitrite levels using HPLC and 8-hydroxydeoxyguanosine adduct using ELISA, indicative of endogenous NO production and reactive oxygen species (ROS) production, respectively. Jejunal transcriptional levels of iNOS, neuronal NO synthase (nNOS), and interferon-␥ (IFN-␥) were also determined by RT-PCR. Fasting caused significant jejunal mucosal atrophy due to attenuated cell proliferation and enhanced apoptosis with increase in iNOS transcription, its protein expression in intestinal epithelial cells (IEC), and jejunal nitrite levels. However, AG treatment histologically reduced apoptosis with inhibition of fastinginduced iNOS transcription, protein expression, and nitrite production. We also observed fasting-induced ROS production and subsequent IFN-␥ transcription, which were all inhibited by AG treatment. Furthermore, we observed reduced transcriptional levels of nNOS, known to suppress iNOS activation physiologically. These results suggest that fasting-induced iNOS activation in IEC may induce apoptosis mediators such as IFN-␥ via a ROS-mediated mechanism and also a possible role of nNOS in the regulation of iNOS activity in fasting-induced apoptosis.aminoguanidine; reactive oxygen species; intestinal epithelial cells; neuronal nitric oxide synthase THE GASTROINTESTINAL EPITHELIUM is a dynamic tissue characterized by a high cellular turnover rate with a balance between cell proliferation and cell apoptosis, consequently leading to renewal of the entire intestinal epithelium every 3-5 days (9,19). This single layer of cells lining the gut lumen acts as a barrier against harmful intraluminal entities, including foreign antigens, microorganisms, and toxins, and also acts as a selective filter allowing the translocation of essential dietary nutrients, electrolytes, and water. However, these physiological functions are occasionally impaired under pathological conditions such as inflammation and ischemia-reperfusion and are accompanied by intestinal histological changes, including apoptosis.Fasting is likely a physiological challenge evoking a response to the absence of luminal nutrients by functional and morphological changes, including intestinal epithe...

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Section: Body Weight Changesmentioning

confidence: 99%

Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

Ito

Uchida

Yokote

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…4 Enteral starvation and total parenteral nutrition, as applied to critically ill patients, are reported to result in increased gut wall permeability, a compromised immune system, and bacterial translocation. [5][6][7][8][9][10] Because autophagy, a process induced on starvation, [11][12][13] influences the generation of Paneth cell granules, 14 we hypothesize that enteral starvation impairs Paneth cell function, contributing to starvation-associated gut compromise.…”

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confidence: 99%

Starvation Compromises Paneth Cells

Hodin

Lenaerts

Grootjans

et al. 2011

The American Journal of Pathology

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The intestine is challenged with the task of protecting the body's internal milieu against bacterial invasion. To this end, the gut is equipped with an epithelial lining connected by tight junctions, a mucus layer, gut-associated lymphoid tissue, and Paneth cells. Paneth cells are highly specialized epithelial cells located in the crypts of the small intestine, and play an important role in gut innate immunity. 1 These cells sense bacterial presence and secrete granules containing antimicrobial peptides, including lysozyme, RegIII␥, and cryptdins (the murine counterparts of human ␣-defensins) both constitutively and in response to activation by bacteria or their products. 2 Using a murine cell ablation model, Paneth cells were shown to be crucial in host protection against invasion of both commensal and pathogenic microbiota. 3 In addition, our group has recently shown the additive importance of Paneth cells in preventing bacterial translocation in situations of physical intestinal barrier loss. 4 Enteral starvation and total parenteral nutrition, as applied to critically ill patients, are reported to result in increased gut wall permeability, a compromised immune system, and bacterial translocation. 5-10 Because autophagy, a process induced on starvation, 11-13 influences the generation of Paneth cell granules, 14 we hypothesize that enteral starvation impairs Paneth cell function, contributing to starvation-associated gut compromise.In this study, the effects of food deprivation on Paneth cell function were investigated using a mouse starvation model. We provide evidence that lack of enteral feeding results in Paneth cell autophagy, decreased expression of antimicrobial products (ie, lysozyme, cryptdin, and RegIII␥), and the presence of atypical secretory granules. Our results propose compromised Paneth cells to be involved in the reduced protection against bacterial translocation in enteral starvation.

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“…Interestingly, our mouse TPN model represents a state of increased TNF-␣ expression, as well as increased IEC apoptosis and reduced IEC proliferation (30,33,34). This model, therefore, offers a unique opportunity to study mechanisms contributing to villus atrophy in the absence of overt inflammatory changes or epithelial destruction in inflammatory bowel disease models.…”

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confidence: 99%

Epidermal growth factor/TNF-α transactivation modulates epithelial cell proliferation and apoptosis in a mouse model of parenteral nutrition

Yang

Teitelbaum

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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107

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Feng Y, Teitelbaum DH. Epidermal growth factor/TNF-␣ transactivation modulates epithelial cell proliferation and apoptosis in a mouse model of parenteral nutrition. Am J Physiol Gastrointest Liver Physiol 302: G236 -G249, 2012. First published November 10, 2011; doi:10.1152/ajpgi.00142.2011.-Epidermal growth factor (EGF) and tumor necrosis factor-␣ (TNF-␣) signaling are critical for effective proliferative and apoptotic actions; however, little is known about the codependency of these signaling pathways in the intestinal epithelium. Because total parenteral nutrition (TPN) is associated with loss of intestinal epithelial cell (IEC) proliferation and increased apoptosis, we utilized a mouse model to explore these transactivation pathways in small bowel epithelium. Mice underwent intravenous cannulation and were given enteral nutrition or TPN for 7 days. Outcomes included IEC proliferation, apoptosis, and survival. To address transactivation or dependence of EGF and TNF on IEC physiology, TNF-␣ receptor knockout (KO) mice, TNFR1-KO, R2-KO, or R1R2-double KO, were used. Exogenous EGF and pharmacological blockade of ErbB1 were performed in other groups to examine the relevance of the ErB1 pathway. TPN increased IEC TNFR1 and decreased EGF and ErbB1 abundance. Loss of IEC proliferation was prevented by exogenous EGF or blockade of TNFR1. However, EGF action was prevented without effective TNFR2 signaling. Also, blockade of TNFR1 could not prevent loss of IEC proliferation without effective ErbB1 signaling. TPN increased IEC apoptosis and was due to increased TNFR1 signaling. Exogenous EGF or blockade of TNFR1 could prevent increased apoptosis, and both pathways were dependent on effective ErbB1 signaling. Exogenous EGF prevented increased apoptosis in mice lacking TNFR2 signaling. TPN mice had significantly decreased survival vs. controls, and this was associated with the TNFR1 signaling pathway. We concluded that these findings identify critical mechanisms that contribute to TPN-associated mucosal atrophy via altered TNF-␣/EGF signaling. It emphasizes the importance of both TNFR1 and TNFR2 pathways, as well as the strong interdependence on an intact EGF/ErbB1 pathway.

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Lack of enteral nutrition—effects on the intestinal immune system

Cited by 114 publications

References 33 publications

Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

Starvation Compromises Paneth Cells

Epidermal growth factor/TNF-α transactivation modulates epithelial cell proliferation and apoptosis in a mouse model of parenteral nutrition

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