SemOpenAlex |

SemOpenAlex

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1980688962> ?p ?o ?g. }

Showing items 1 to 54 of 54 with 100 items per page.

W1980688962 endingPage "1274" @default.
W1980688962 startingPage "1273" @default.
W1980688962 abstract "Yang H, Fan Y, Teitelbaum DH (Department of Surgery, University of Michigan Medical School and CS Mott Children’s Hospital, Ann Arbor, Michigan). Intraepithelial lymphocyte-derived interferon-gamma evokes enterocyte apoptosis with parenteral nutrition in mice. Am J Physiol Gastrointest Liver Physiol 2003;284:G629–G637.The homeostatic balance between the rate of cell production and cell death is especially pertinent in the intestine because the rates of enterocyte turnover are extremely high. Total parenteral nutrition (TPN) is associated with the development of intestinal mucosal atrophy. This atrophy might possibly play a role in attenuating the intestinal barrier to bacteria and bacterial products, thus contributing toward an increased risk for sepsis and/or liver injury in parenterally fed patients. It is therefore clinically relevant to more fully understand how TPN perturbs the vital balance of enterocyte turnover to promote intestinal mucosal atrophy.In addition to reduced enterocyte proliferation, TPN is associated with elevated rates of enterocyte apoptosis (J Nutr 2002;132:2010–2014). In a recent report, Teitelbaum et al. provide an important new insight into the pathogenesis of intestinal mucosal atrophy by exploring a potential mechanism for the TPN-associated accelerated enterocyte apoptosis (Am J Physiol Gastrointest Liver Physiol 2003;284:G629–G637). In this study, they expand on their prior observations of increased interferon gamma (IFN-γ) messenger RNA expression within intraepithelial lymphocytes (IEL) harvested from the intestine of mice receiving TPN (J Surg Res 1998;79:91–96). They specifically test the hypothesis that the increased IEL expression of IFN-γ activates enterocyte apoptosis. In addition, they explore the notion that the apoptosis activation by IFN-γ occurs via the Fas/FasL system.In the first series of experiments, TPN or crystalloid solution was intravenously infused to mice for 7 days. In the control group, standard laboratory chow and water were provided ad libitum. The animals in both groups were estimated to have received similar calories. Mucosal atrophy was confirmed by a 32% decrease in the jejunal villus height from the animals receiving TPN. In addition, TPN was associated with a 45% reduction in rates of enterocyte proliferation and a 3-fold increase in enterocyte apoptosis.Next, IEL expression of IFN-γ protein was measured by enzyme-linked immunosorbent assay and found to be 3.5-fold higher in the TPN group. Using flow cytometry, the investigators further characterized the IEL subpopulations and found that TPN significantly increased the IFN-γ expression within CD8+ and CD3+, but not CD4+, cells. Finally, whereas Fas expression was found to be unchanged, the expression of FasL in the TPN animals was found to be significantly elevated. To determine whether enterocytes (expressing Fas) were more vulnerable to apoptosis induced by IEL-derived FasL expression, enterocytes were isolated from TPN and control mice and incubated with an anti-Fas antibody. The engagement of Fas by this antibody resulted in higher rates of enterocyte apoptosis from the TPN mice versus the control group.In the next series of experiments, TPN was administered to IFN-γ null and wild-type mice. In the absence of IFN-γ expression, villus heights were taller and TPN did not activate enterocyte apoptosis to the same degree as in the control group. Further, the expected induction of FasL expression by TPN within IELs of the IFN-γ null mice did not occur. In addition, the induction of apoptosis by anti-Fas antibody in isolated enterocytes derived from the IFN-γ null mice was higher when compared with controls.In the final experiments, TPN was given to mice deficient in either Fas (lpr) or FasL ( gld) expression. Rates of apoptosis in these 2 different mice strains were significantly lower when compared with the wild-type mice. Further, villus heights were greater in both strains when compared with the control mice given TPN.CommentThese elegant studies provide important mechanistic insight into the pathogenesis of increased enterocyte apoptosis and mucosal atrophy that occurs in association with TPN. The experimental techniques are sophisticated and well designed, and make a strong case for INF-γ and enterocyte death receptor engagement (particularly Fas and IEL-derived FasL) as primary mediators of apoptosis activation.Several points should be considered in the interpretation of the data from this report. In comparison with wild-type mice, TPN was associated with reduced enterocyte apoptosis in each of the strains of mice deficient in the expression of IFN-γ, Fas, or FasL. However, rates of apoptosis were not completely normalized when compared with control animals not receiving TPN. This would suggest (as the investigators appropriately discuss) that perhaps other death receptor–mediated pathways such as tumor necrosis factor may be involved to direct enterocyte apoptosis. What was not mentioned is the role for the intrinsic (non–death receptor) pathway in this model of increased enterocyte apoptosis. In particular, the execution of apoptosis may be significantly affected by alterations in the expression of various bcl-2 family members. Another experimental paradigm for increased enterocyte apoptosis is the adaptation response of the remnant bowel to massive intestinal resection (J Gastrointest Surg 1998;2:44–49). Under these conditions, the expression of the proapoptotic gene bax is increased simultaneously with a reduced expression of the anti-apoptosis gene bcl-w (J Gastrointest Surg 2000;4:93–100). Further, the activation of enterocyte apoptosis after intestinal resection is prevented in bax-null mice (Surgery 2000;128:165–170). Therefore, it may be informative to monitor altered expression profiles of the various bcl-2 homologues during parenteral nutrition in this model.In addition to local proapoptotic factors within the intestine, the genesis of TPN-associated mucosal atrophy may be caused by reduced secretion of multiple enterotrophic endocrine and exocrine-derived peptides and growth factors that are up-regulated in response to oral feeding. Thus, it should be considered that the absence of a luminal or endocrine prosurvival growth factor or peptide (as opposed to the local production of a proapoptotic ligand as proposed in this study) may be more decisive in the genesis of atrophy. Even without endocrine/exocrine secretion, enteral nutrition alone probably accounts, at least in part, for the decreasing gradient of intestinal mucosal thickness that occurs from the duodenum to the terminal ileum. Along these lines, the authors compared mice that were parenterally fed with mice that were fed the same calories enterally. It is therefore impossible to determine whether the reported findings were caused by lack of trophic luminal nutrient, diminished trophic endocrine/exocrine secretion because of no oral feeding, or even the parenteral nutrition solution. An additional experimental group of animals receiving intravenous crystalloid solution, but no oral intake, might have been useful.While beyond the scope of the current study, which focuses on the regulation of apoptosis, consideration must be afforded to the effect that TPN has on rates of enterocyte proliferation. Because the investigators showed significantly reduced rates of proliferation in normal mice receiving TPN, it is unclear as to the magnitude that this perturbation undoubtedly contributes toward the development of intestinal mucosal atrophy. Similarly, altered rates of enterocyte proliferation might have accounted for the intestinal phenotype observed in the mice deficient in IFN-γ, Fas, or FasL expression. It would be interesting to compare rates of enterocyte proliferation in these mice with the wild-type mice receiving TPN.Finally, it is presently unclear as to whether the changes in inflammation and/or apoptosis described in the present report are the cause or effect of the intestinal mucosal atrophy. The investigators imply that these alterations are fundamental toward the development of mucosal atrophy. However, the animals were studied only after the atrophy had already taken place. The atrophic mucosa would predictably be more susceptible to the translocation of bacteria and/or bacterial products from the intestinal lumen. As such, it would not be surprising that extrinsic death receptor activation is involved in enterocyte apoptosis once the atrophy had already developed. Future studies at earlier time points to link the timing of IFN-γ, Fas, or FasL expression, increased apoptosis, and the development of mucosal atrophy will be critical to elucidate more fully the pathogenesis of intestinal mucosal atrophy associated with parenteral nutrition. Yang H, Fan Y, Teitelbaum DH (Department of Surgery, University of Michigan Medical School and CS Mott Children’s Hospital, Ann Arbor, Michigan). Intraepithelial lymphocyte-derived interferon-gamma evokes enterocyte apoptosis with parenteral nutrition in mice. Am J Physiol Gastrointest Liver Physiol 2003;284:G629–G637. The homeostatic balance between the rate of cell production and cell death is especially pertinent in the intestine because the rates of enterocyte turnover are extremely high. Total parenteral nutrition (TPN) is associated with the development of intestinal mucosal atrophy. This atrophy might possibly play a role in attenuating the intestinal barrier to bacteria and bacterial products, thus contributing toward an increased risk for sepsis and/or liver injury in parenterally fed patients. It is therefore clinically relevant to more fully understand how TPN perturbs the vital balance of enterocyte turnover to promote intestinal mucosal atrophy. In addition to reduced enterocyte proliferation, TPN is associated with elevated rates of enterocyte apoptosis (J Nutr 2002;132:2010–2014). In a recent report, Teitelbaum et al. provide an important new insight into the pathogenesis of intestinal mucosal atrophy by exploring a potential mechanism for the TPN-associated accelerated enterocyte apoptosis (Am J Physiol Gastrointest Liver Physiol 2003;284:G629–G637). In this study, they expand on their prior observations of increased interferon gamma (IFN-γ) messenger RNA expression within intraepithelial lymphocytes (IEL) harvested from the intestine of mice receiving TPN (J Surg Res 1998;79:91–96). They specifically test the hypothesis that the increased IEL expression of IFN-γ activates enterocyte apoptosis. In addition, they explore the notion that the apoptosis activation by IFN-γ occurs via the Fas/FasL system. In the first series of experiments, TPN or crystalloid solution was intravenously infused to mice for 7 days. In the control group, standard laboratory chow and water were provided ad libitum. The animals in both groups were estimated to have received similar calories. Mucosal atrophy was confirmed by a 32% decrease in the jejunal villus height from the animals receiving TPN. In addition, TPN was associated with a 45% reduction in rates of enterocyte proliferation and a 3-fold increase in enterocyte apoptosis. Next, IEL expression of IFN-γ protein was measured by enzyme-linked immunosorbent assay and found to be 3.5-fold higher in the TPN group. Using flow cytometry, the investigators further characterized the IEL subpopulations and found that TPN significantly increased the IFN-γ expression within CD8+ and CD3+, but not CD4+, cells. Finally, whereas Fas expression was found to be unchanged, the expression of FasL in the TPN animals was found to be significantly elevated. To determine whether enterocytes (expressing Fas) were more vulnerable to apoptosis induced by IEL-derived FasL expression, enterocytes were isolated from TPN and control mice and incubated with an anti-Fas antibody. The engagement of Fas by this antibody resulted in higher rates of enterocyte apoptosis from the TPN mice versus the control group. In the next series of experiments, TPN was administered to IFN-γ null and wild-type mice. In the absence of IFN-γ expression, villus heights were taller and TPN did not activate enterocyte apoptosis to the same degree as in the control group. Further, the expected induction of FasL expression by TPN within IELs of the IFN-γ null mice did not occur. In addition, the induction of apoptosis by anti-Fas antibody in isolated enterocytes derived from the IFN-γ null mice was higher when compared with controls. In the final experiments, TPN was given to mice deficient in either Fas (lpr) or FasL ( gld) expression. Rates of apoptosis in these 2 different mice strains were significantly lower when compared with the wild-type mice. Further, villus heights were greater in both strains when compared with the control mice given TPN. CommentThese elegant studies provide important mechanistic insight into the pathogenesis of increased enterocyte apoptosis and mucosal atrophy that occurs in association with TPN. The experimental techniques are sophisticated and well designed, and make a strong case for INF-γ and enterocyte death receptor engagement (particularly Fas and IEL-derived FasL) as primary mediators of apoptosis activation.Several points should be considered in the interpretation of the data from this report. In comparison with wild-type mice, TPN was associated with reduced enterocyte apoptosis in each of the strains of mice deficient in the expression of IFN-γ, Fas, or FasL. However, rates of apoptosis were not completely normalized when compared with control animals not receiving TPN. This would suggest (as the investigators appropriately discuss) that perhaps other death receptor–mediated pathways such as tumor necrosis factor may be involved to direct enterocyte apoptosis. What was not mentioned is the role for the intrinsic (non–death receptor) pathway in this model of increased enterocyte apoptosis. In particular, the execution of apoptosis may be significantly affected by alterations in the expression of various bcl-2 family members. Another experimental paradigm for increased enterocyte apoptosis is the adaptation response of the remnant bowel to massive intestinal resection (J Gastrointest Surg 1998;2:44–49). Under these conditions, the expression of the proapoptotic gene bax is increased simultaneously with a reduced expression of the anti-apoptosis gene bcl-w (J Gastrointest Surg 2000;4:93–100). Further, the activation of enterocyte apoptosis after intestinal resection is prevented in bax-null mice (Surgery 2000;128:165–170). Therefore, it may be informative to monitor altered expression profiles of the various bcl-2 homologues during parenteral nutrition in this model.In addition to local proapoptotic factors within the intestine, the genesis of TPN-associated mucosal atrophy may be caused by reduced secretion of multiple enterotrophic endocrine and exocrine-derived peptides and growth factors that are up-regulated in response to oral feeding. Thus, it should be considered that the absence of a luminal or endocrine prosurvival growth factor or peptide (as opposed to the local production of a proapoptotic ligand as proposed in this study) may be more decisive in the genesis of atrophy. Even without endocrine/exocrine secretion, enteral nutrition alone probably accounts, at least in part, for the decreasing gradient of intestinal mucosal thickness that occurs from the duodenum to the terminal ileum. Along these lines, the authors compared mice that were parenterally fed with mice that were fed the same calories enterally. It is therefore impossible to determine whether the reported findings were caused by lack of trophic luminal nutrient, diminished trophic endocrine/exocrine secretion because of no oral feeding, or even the parenteral nutrition solution. An additional experimental group of animals receiving intravenous crystalloid solution, but no oral intake, might have been useful.While beyond the scope of the current study, which focuses on the regulation of apoptosis, consideration must be afforded to the effect that TPN has on rates of enterocyte proliferation. Because the investigators showed significantly reduced rates of proliferation in normal mice receiving TPN, it is unclear as to the magnitude that this perturbation undoubtedly contributes toward the development of intestinal mucosal atrophy. Similarly, altered rates of enterocyte proliferation might have accounted for the intestinal phenotype observed in the mice deficient in IFN-γ, Fas, or FasL expression. It would be interesting to compare rates of enterocyte proliferation in these mice with the wild-type mice receiving TPN.Finally, it is presently unclear as to whether the changes in inflammation and/or apoptosis described in the present report are the cause or effect of the intestinal mucosal atrophy. The investigators imply that these alterations are fundamental toward the development of mucosal atrophy. However, the animals were studied only after the atrophy had already taken place. The atrophic mucosa would predictably be more susceptible to the translocation of bacteria and/or bacterial products from the intestinal lumen. As such, it would not be surprising that extrinsic death receptor activation is involved in enterocyte apoptosis once the atrophy had already developed. Future studies at earlier time points to link the timing of IFN-γ, Fas, or FasL expression, increased apoptosis, and the development of mucosal atrophy will be critical to elucidate more fully the pathogenesis of intestinal mucosal atrophy associated with parenteral nutrition. These elegant studies provide important mechanistic insight into the pathogenesis of increased enterocyte apoptosis and mucosal atrophy that occurs in association with TPN. The experimental techniques are sophisticated and well designed, and make a strong case for INF-γ and enterocyte death receptor engagement (particularly Fas and IEL-derived FasL) as primary mediators of apoptosis activation. Several points should be considered in the interpretation of the data from this report. In comparison with wild-type mice, TPN was associated with reduced enterocyte apoptosis in each of the strains of mice deficient in the expression of IFN-γ, Fas, or FasL. However, rates of apoptosis were not completely normalized when compared with control animals not receiving TPN. This would suggest (as the investigators appropriately discuss) that perhaps other death receptor–mediated pathways such as tumor necrosis factor may be involved to direct enterocyte apoptosis. What was not mentioned is the role for the intrinsic (non–death receptor) pathway in this model of increased enterocyte apoptosis. In particular, the execution of apoptosis may be significantly affected by alterations in the expression of various bcl-2 family members. Another experimental paradigm for increased enterocyte apoptosis is the adaptation response of the remnant bowel to massive intestinal resection (J Gastrointest Surg 1998;2:44–49). Under these conditions, the expression of the proapoptotic gene bax is increased simultaneously with a reduced expression of the anti-apoptosis gene bcl-w (J Gastrointest Surg 2000;4:93–100). Further, the activation of enterocyte apoptosis after intestinal resection is prevented in bax-null mice (Surgery 2000;128:165–170). Therefore, it may be informative to monitor altered expression profiles of the various bcl-2 homologues during parenteral nutrition in this model. In addition to local proapoptotic factors within the intestine, the genesis of TPN-associated mucosal atrophy may be caused by reduced secretion of multiple enterotrophic endocrine and exocrine-derived peptides and growth factors that are up-regulated in response to oral feeding. Thus, it should be considered that the absence of a luminal or endocrine prosurvival growth factor or peptide (as opposed to the local production of a proapoptotic ligand as proposed in this study) may be more decisive in the genesis of atrophy. Even without endocrine/exocrine secretion, enteral nutrition alone probably accounts, at least in part, for the decreasing gradient of intestinal mucosal thickness that occurs from the duodenum to the terminal ileum. Along these lines, the authors compared mice that were parenterally fed with mice that were fed the same calories enterally. It is therefore impossible to determine whether the reported findings were caused by lack of trophic luminal nutrient, diminished trophic endocrine/exocrine secretion because of no oral feeding, or even the parenteral nutrition solution. An additional experimental group of animals receiving intravenous crystalloid solution, but no oral intake, might have been useful. While beyond the scope of the current study, which focuses on the regulation of apoptosis, consideration must be afforded to the effect that TPN has on rates of enterocyte proliferation. Because the investigators showed significantly reduced rates of proliferation in normal mice receiving TPN, it is unclear as to the magnitude that this perturbation undoubtedly contributes toward the development of intestinal mucosal atrophy. Similarly, altered rates of enterocyte proliferation might have accounted for the intestinal phenotype observed in the mice deficient in IFN-γ, Fas, or FasL expression. It would be interesting to compare rates of enterocyte proliferation in these mice with the wild-type mice receiving TPN. Finally, it is presently unclear as to whether the changes in inflammation and/or apoptosis described in the present report are the cause or effect of the intestinal mucosal atrophy. The investigators imply that these alterations are fundamental toward the development of mucosal atrophy. However, the animals were studied only after the atrophy had already taken place. The atrophic mucosa would predictably be more susceptible to the translocation of bacteria and/or bacterial products from the intestinal lumen. As such, it would not be surprising that extrinsic death receptor activation is involved in enterocyte apoptosis once the atrophy had already developed. Future studies at earlier time points to link the timing of IFN-γ, Fas, or FasL expression, increased apoptosis, and the development of mucosal atrophy will be critical to elucidate more fully the pathogenesis of intestinal mucosal atrophy associated with parenteral nutrition. ReplyGastroenterologyVol. 125Issue 4Preview Full-Text PDF" @default.
W1980688962 created "2016-06-24" @default.
W1980688962 creator A5073997035 @default.
W1980688962 date "2003-10-01" @default.
W1980688962 modified "2023-09-26" @default.
W1980688962 title "Enterocyte apoptosis and TPN-associated intestinal mucosal atrophy: a view of the chicken or the egg?" @default.
W1980688962 doi "https://doi.org/10.1016/j.gastro.2003.04.002" @default.
W1980688962 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15108717" @default.
W1980688962 hasPublicationYear "2003" @default.
W1980688962 type Work @default.
W1980688962 sameAs 1980688962 @default.
W1980688962 citedByCount "2" @default.
W1980688962 crossrefType "journal-article" @default.
W1980688962 hasAuthorship W1980688962A5073997035 @default.
W1980688962 hasConcept C126322002 @default.
W1980688962 hasConcept C142724271 @default.
W1980688962 hasConcept C190283241 @default.
W1980688962 hasConcept C2777882243 @default.
W1980688962 hasConcept C2779604457 @default.
W1980688962 hasConcept C2781172350 @default.
W1980688962 hasConcept C55493867 @default.
W1980688962 hasConcept C71924100 @default.
W1980688962 hasConcept C86803240 @default.
W1980688962 hasConceptScore W1980688962C126322002 @default.
W1980688962 hasConceptScore W1980688962C142724271 @default.
W1980688962 hasConceptScore W1980688962C190283241 @default.
W1980688962 hasConceptScore W1980688962C2777882243 @default.
W1980688962 hasConceptScore W1980688962C2779604457 @default.
W1980688962 hasConceptScore W1980688962C2781172350 @default.
W1980688962 hasConceptScore W1980688962C55493867 @default.
W1980688962 hasConceptScore W1980688962C71924100 @default.
W1980688962 hasConceptScore W1980688962C86803240 @default.
W1980688962 hasIssue "4" @default.
W1980688962 hasLocation W19806889621 @default.
W1980688962 hasLocation W19806889622 @default.
W1980688962 hasOpenAccess W1980688962 @default.
W1980688962 hasPrimaryLocation W19806889621 @default.
W1980688962 hasRelatedWork W1966119938 @default.
W1980688962 hasRelatedWork W1975675339 @default.
W1980688962 hasRelatedWork W2037655651 @default.
W1980688962 hasRelatedWork W2054565847 @default.
W1980688962 hasRelatedWork W2066179908 @default.
W1980688962 hasRelatedWork W2072984176 @default.
W1980688962 hasRelatedWork W2087623513 @default.
W1980688962 hasRelatedWork W2147130570 @default.
W1980688962 hasRelatedWork W2398838020 @default.
W1980688962 hasRelatedWork W2767432620 @default.
W1980688962 hasVolume "125" @default.
W1980688962 isParatext "false" @default.
W1980688962 isRetracted "false" @default.
W1980688962 magId "1980688962" @default.
W1980688962 workType "article" @default.