Intraepithelial lymphocyte-derived interferon-γ evokes enterocyte apoptosis with parenteral nutrition in mice

Yang, Hua; Fan, Yongyi; Teitelbaum, Daniel H.

doi:10.1152/ajpgi.00290.2002

Cited by 60 publications

(66 citation statements)

References 43 publications

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“…We chose to study KGF expression in two controlled models of epithelial growth: administration of TPN and a SBS model. Administration of TPN results in an altered rate of epithelial turnover, villus atrophy, and loss of epithelial barrier function (43,44). Our study confirmed that TPN decreased EC proliferation and led to villus atrophy.…”

Section: Discussionsupporting

confidence: 81%

Intestinal Intraepithelial Lymphocyte γδ-T Cell-Derived Keratinocyte Growth Factor Modulates Epithelial Growth in the Mouse

Yang

Antony

Wildhaber

et al. 2004

The Journal of Immunology

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116

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Keratinocyte growth factor (KGF) promotes intestinal epithelial growth. To understand the relevance of intraepithelial lymphocyte (IEL)-derived KGF expression on epithelial growth, we used a mouse model of villus atrophy by the administration of total parenteral nutrition, and a model of villus hypertrophy by the creation of a short bowel syndrome. KGF expression was confined to γδ-ΤCR+ IELs. IEL-derived KGF expression was highest in the crypts, somewhat less in the lower portion of villi, and markedly lower in the upper portion of villi. Total parenteral nutrition administration was associated with a down-regulation of IEL-derived KGF expression, and short bowel syndrome was associated with an up-regulation of IEL-derived KGF expression. In the absence of γδ-ΤCR+ IEL, using γδ−/− mice, intestinal epithelial cell proliferation decreased in control, and in both mucosal atrophy (22% decline) and mucosal hypertrophy (14%) models. These results show that KGF from IELs is an important factor for maintenance of intestinal epithelial cell proliferation and villus growth.

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Section: Discussionsupporting

confidence: 81%

Intestinal Intraepithelial Lymphocyte γδ-T Cell-Derived Keratinocyte Growth Factor Modulates Epithelial Growth in the Mouse

Yang

Antony

Wildhaber

et al. 2004

The Journal of Immunology

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116

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“…13). Recent evidence shows that IEL-derived IFN-␥ evokes enterocyte apoptosis via an upregulation of Fas/FasL, leading to the increase in sensitivity of epithelial cells to Fas-mediated apoptosis (30,56) through the type 1 pathway (56). It has been suggested that complex reciprocal interactions exist between IEC and IEL (20,56); therefore, it is likely that IEC and IEL form a reciprocal feedback loop in which iNOS-released NO, physiologically present in IEC, stimulates IFN-␥ production in IEL through a ROS-mediated mechanism (1,5,38), then IFN-␥ stimulates further iNOS-derived NO production, resulting in further IFN-␥ production and subsequent IEC apoptosis (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…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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“…Proinflammation cytokine and chemokine mRNA expression was measured with quantitative PCR (qPCR), and gene expression was represented as relative to ␤-actin, as previously described (12). RNA extraction of muscosal scrapings was as previously described (12,44). Oligomers were designed using an optimization program (www.premierBiosoft.com).…”

Section: Methodsmentioning

confidence: 99%

Homeostasis alteration within small intestinal mucosa after acute enteral refeeding in total parenteral nutrition mouse model

Yang

Barrett

Hou

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Feeding strategies to care for patients who transition from enteral nutrient deprivation while on total parenteral nutrition (TPN) to enteral feedings generally proceed to full enteral nutrition once the gastrointestinal tract recovers; however, an increasing body of literature suggests that a subgroup of patients may actually develop an increased incidence of adverse events, including death. To examine this further, we studied the effects of acute refeeding in a mouse model of TPN. Interestingly, refeeding led to some beneficial effects, including prevention in the decline in intestinal epithelial cell (IEC) proliferation. However, refeeding led to a significant increase in mucosal expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), as well as an upregulation in Toll-like receptor 4 (TLR-4). Refeeding also failed to prevent TPN-associated increases in IEC apoptosis, loss of epithelial barrier function, and failure of the leucine-rich repeat-containing G protein-coupled receptor 5-positive stem cell expression. Transitioning from TPN to enteral feedings led to a partial restoration of the small bowel microbial population. In conclusion, while acute refeeding led to some restoration of normal gastrointestinal physiology, enteral refeeding led to a significant increase in mucosal inflammatory markers and may suggest alternative strategies to enteral refeeding should be considered.

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Intraepithelial lymphocyte-derived interferon-γ evokes enterocyte apoptosis with parenteral nutrition in mice

Cited by 60 publications

References 43 publications

Intestinal Intraepithelial Lymphocyte γδ-T Cell-Derived Keratinocyte Growth Factor Modulates Epithelial Growth in the Mouse

Intestinal Intraepithelial Lymphocyte γδ-T Cell-Derived Keratinocyte Growth Factor Modulates Epithelial Growth in the Mouse

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

Homeostasis alteration within small intestinal mucosa after acute enteral refeeding in total parenteral nutrition mouse model

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