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128 Acute Regulation of Apical Sodium-Dependent Bile Acid Transporter (ASBT) By Dexamethasone in Human Intestinal Epithelial Cells
AGA Abstracts
Na, n=3, p<0.01). Na-dependent adenosine uptake was significantly diminished during chronic enteritis (5.2 ± 0.5 pmol/ug protein in normal, 2.6 ± 0.2 in inflamed, n=3, p<0.01). RTQ-PCR analysis demonstrated that CNT2 mRNA expression was decreased during chronic intestinal inflammation (1.8 ± 0.1 fold, n=3, p<0.01). Methypredisolone (MP) treatment of rabbit with chronic enteritis alleviated the inhibition of Na-dependent adenosine uptake (4.7 ± 0.4 pmol/ug protein, n=3, p<0.01) and CNT2 mRNA expression (1 ± 0.1 fold, n= 3, p<0.01). Conclusions: Na-dependent adenosine uptake is mediated by CNT2 in intestinal villus cells but not crypt cells. Adenosine uptake and CNT2 mRNA expression were significantly inhibited in villus cells during chronic intestinal inflammation. MP reversed the inhibition of adenosine uptake and CNT2 mRNA expression in villus cells during chronic enteritis. These data indicate that inhibition of CNT2 mRNA expression and adenosine absorption in villus cells during chronic intestinal inflammation can be restored by steroid treatment.
129 The Crohn's Disease Candidate Gene Protein Tyrosine Phosphatase N2 (PTPN2) Is Activated By Gamma Interferon (IFNγ) in Intestinal Epithelial Cells (IECs) in An Adenosine-Monophosphate Kinase (Ampk) Dependent Manner Michael Scharl, Kim E. Barrett, Declan F. McCole Background: PTPN2 has recently been identified as a Crohn's disease (CD) candidate gene. This phosphatase dephosphorylates and inactivates proinflammatory modulators, such as the Signal Transducer and Activator of Transcription 1 (STAT1). IFNγ plays a major role in chronic inflammatory processes, such as CD, and many of its effects are mediated by STAT1. Therefore, PTPN2 could pivotally regulate inflammatory processes in the intestine. The cellular energy sensor, AMPK, has been shown to activate PTPN2 in human fibroblasts. Here, we investigate the role of PTPN2 in a model of intestinal inflammation using T84 intestinal epithelial cells. Methods: Protein analysis was performed by Western blot and RNA analysis by RT-PCR. PTPN2 activity was assessed by a fluorescent phosphatase assay and subcellular PTPN2 distribution by confocal microscopy. PTPN2 knock down was induced by siRNA. Results: Expression of PTPN2 mRNA was increased by IFNγ treatment of T84 monolayers (1000 U/ml), (p<0.01, n=3, 24-72h). Furthermore, IFNγ increased cytoplasmic (p<0.01, n=4, 48-72h) and nuclear (p<0.01, n=4, 24h) levels of PTPN2 protein as well as cytoplasmic PTPN2 phosphatase activity (p<0.05, n=4, 72h). IFNγ also altered the subcellular distribution of PTPN2, causing a cytoplasmic accumulation, that was prominent at 72h. Phosphorylation of STAT1 was reduced in parallel to the increase in PTPN2 activity (p<0.001, n=4, 24h vs. 72h). siRNA mediated knock-down of PTPN2 significantly enhanced IFNγinduced STAT1 phosphorylation (p<0.001, n=3, 24h). IFNγ increased AMPK activity as assessed by its phosphorylation (p<0.01, n=3, 6h). Inhibition of AMPK with Compound C (50 µM) decreased cytoplasmic (p<0.05, n=4, 72h) and nuclear (p<0.05, n=4, 72h) PTPN2 levels, and increased STAT1 phosphorylation in response to IFNγ (p<0.001, n=4, 24h). Cytoplasmic accumulation of PTPN2 was likewise impaired. However, AMPK activation with AICA-riboside-5'-phosphate (1 mM) affected neither PTPN2 expression nor STAT1 phosphorylation. Conclusion: Thus, the expression and activity of the CD candidate gene PTPN2 is increased by IFNγ. This occurs, at least in part, through AMPK, although AMPK alone is not sufficient for the response. Activated PTPN2 in turn reduces STAT1-mediated proinflammatory signal transduction in IECs. These data demonstrate a novel role for AMPKdependent activation of PTPN2 in the downregulation of proinflammatory signalling in a cellular model of intestinal inflammation. These findings support the hypothesis, that dysfunction of PTPN2 contributes to chronic inflammatory processes in the intestine, such as CD. Supported by the Crohn's and Colitis Foundation of America and NIH.
127 Bile Acids Decrease Ileal Mucin During Development of Experimental Necrotizing Enterocolitis Charity A. Reynolds, Ludmila Khailova, Bohuslav Dvorak, Kelly M. Arganbright, Melissa Halpern Background: Bile acids (BAs) facilitate digestion and transport of fats and sterols in the intestine and liver. However, accumulation of BAs in the intestine can result in damage to the intestinal epithelium. Using the neonatal rat model of necrotizing enterocolitis (NEC), we have previously shown that BAs accumulate in both the ileal lumen and enterocytes and these increased BA levels are positively correlated with disease severity. Importantly, when BAs are not allowed to accumulate, neonatal rat pups develop significantly less disease. Intestinal mucins protect the epithelial surface by forming a semi-permeable mucous layer between the lumen and the intestinal epithelium. In premature infants, a deficiency in the mucous layer has been suggested to contribute to intestinal injury during NEC. Muc2, the predominant secretory mucin produced by intestinal goblet cells, has been shown to be altered by BAs and transport of BAs via mucin is a critical step in normal fat absorption. Objective: To determine if BAs affect mucin production during the development of experimental NEC. Methods: Newborn Sprague-Dawley rats were divided into the following groups: DF (n=12), pups allowed to feed from the mother for 4 days and exposed to asphyxia and cold stress; NEC (n=12), pups hand-fed with formula for 4 days and exposed to asphyxia and cold stress, NEC + Chol (n=12); pups hand-fed with formula for 4 days, asphyxia and cold stressed and given 120 mg/kg/day cholestyramine to eliminate ileal BA; BA Gav (n= 5), newborn rats gavaged with 20mM Na deoxycholic acid twice per day for 2 days and Control (n=5), newborn rats gavaged with vehicle only. Muc2 positive cells were enumerated after immunohistological staining by counting positive cells per 100 intestinal epithelial cells. Results: Animals in the NEC group (median ileal damage score 2.5; NEC incidence 70%) had significantly lower numbers of Muc2+ cells than DF littermates (median damage score 0, NEC incidence 0%). In the NEC+Chol group (median damage score 1.5; NEC incidence 20%, p ≤ 0.01 vs NEC), where luminal BAs were prevented from accumulating, numbers of Muc2+ cells were signficantly increased compared to the NEC group. When exogenous BAs were introduced into the GI tract (BA Gav), numbers of Muc2+ cells were significantly reduced compared to animals given vehicle alone (Control). Conclusions: Increased ileal BAs result in decreased mucin production in neonatal rat intestine. Fewer Muc2+ cells may decrease transport of BAs independent of changes in active transport mechanisms, contributing to BA accumulation in the intestine and subsequent ileal barrier dysfunction.
130 Activated Innate Immune System in Irritable Bowel Syndrome? Jost Langhorst, Angela Junge, Andreas Rueffer, Jan Wehkamp, Dirk Foell, Andreas Michalsen, Frauke Musial, Gustav J. Dobos Background: Human defensins appear to be part of the innate immune system. Human βdefensin-2 (HBD-2) was the first inducible human anti-microbial protein discovered. It can be induced by probiotic microorganisms and pro-inflammatory cytokines. Recent results suggest, that HBD-2 is expressed in active intestinal inflammation, especially in ulcerative colitis (UC). Our aim was to evaluate fecal measurements of HBD-2 in patients with UC as well as irritable bowel syndrome (IBS) and healthy controls (HC). We expected that fecal HBD-2 levels would only be elevated in UC due to its inflammatory pathophysiology. Methods: Fecal specimens were collected from a total of 100 participants (30 with active UC, 47 IBS and 23 HC). Exclusion criterion was the current use of probiotics. Furthermore, IBS patients with elevated CRP or leukocytes, a history of bacterial overgrowth or infectious gastrointestinal disease over the last 6 month were excluded. Disease status was addressed in all participating subjects by medical history and current symptoms. In addition, each IBS and UC patient underwent ileocolonoscopy with histopathology. Fecal inflammation markers Lactoferrin (LF) and Calprotectin (Cal) were measured by ELISA and reported as µg/g. Fecal HBD-2 was measured by ELISA and reported as ng/g feces. Paraffin-embedded tissue from colonic biopsies was tested for HBD-2 peptides by immunohistochemistry. Results: LF as well as Cal was elevated in active UC (Mean: 152.1 ± S.E. 374.7 µg/g; 103.5 ± 87.1 µg/g), compared to IBS (8.4 ± 0.5 µg/g; 18.7 ± 23.1 µg/g), and healthy controls (0.4 ± 0.5 µg/g; 6.6 ± 5.0 µg/g). Scheffe post hoc tests revealed significant differences (p = 0.006) between active UC vs. IBS and HC. To the contrary, HBD-2 levels were highest in active UC (Mean: 106.9 ± S.E. 91.5 ng/g), almost as high in IBS (pts 74.9 ± 58.9 ng/g), and lowest for healthy controls (31.0 ± 15.4 ng/g). Scheffe post hoc tests revealed significant differences (p = 0.001) between the groups of patients (UC and IBS) vs. healthy controls. Immunohistochemical investigation was consistent with fecal secretion data and demonstrated the presence of βdefensin-2 peptides in colonic epithelial enterocytes in UC as well as IBS patients with elevated fecal HBD-2. Conclusions: The results imply, to the contrary to our hypothesis, that fecal levels of HBD-2 were significantly elevated in patients with IBS compared to healthy controls and similar to those in UC patients. The results suggest an activation of the mucosal innate defence system towards a proinflammatory response in IBS patients in the absence of macroscopic signs of inflammation.
128 Acute Regulation of Apical Sodium-Dependent Bile Acid Transporter (ASBT) By Dexamethasone in Human Intestinal Epithelial Cells Pradeep Kumar, Fadi Annaba, Seema Saksena, Pradeep K. Dudeja, Krishnamurthy Ramaswamy, Ravinder K. Gill, Waddah A. Alrefai Ileal apical ASBT mediates intestinal absorption of bile acids and is subject to extensive regulation. ASBT expression has been shown to be up-regulated by various stimuli such as glucocorticoids via transcriptional mechanisms. However, little is known about acute modulation of ASBT in the human intestine. Recent studies have shown that some of the biological effects of glucocorticoids occur in a transcription-independent manner. Therefore, the current studies were designed to examine the short-term effect of dexamethasone on ASBT activity and membrane protein expression. Human intestinal Caco2 cells were transiently cotransfected by electroporation (Amaxa) with expression vectors for human hASBT-V5 fusion protein and human glucocorticoid receptor (GR). The activity of ASBT was assessed by the measurement of Na+-dependent 3H-tuarocholic acid uptake. hASBT-V5 expression on apical membrane was determined by cell surface biotinylation. GR activation by dexamethasone significantly increased hASBT activity in a dose- and time-dependent manner. The maximum induction (an increase by 86.83 ± 18.9 % of control) occurred at 2 h incubation with 1 microM concentration of dexamethasone. This effect was completely abrogated in the presence of 0.5 microM of GR antagonist, RU-486 confirming the involvement of GR. Dexamethasoneinduced increase in ASBT activity appears to be mediated via activation of PI3 kinasedependent pathways since it was blocked in the presence of PI3 kinase inhibitors LY294002 (50 microM) and Wortmanin (5 microM). Parallel to the stimulation in its activity, the level of ASBT-V5 fusion protein expression on apical membrane of Caco2 cells was significantly increased (~ 60%) by dexamethasone. Conclusion: Our data show that dexamethsoneinduced stimulation of hASBT activity occurs via the activation of GR and PI3k-dependent pathways and is associated with an increase in its protein level on the membrane. Our studies provide new insights into short-term regulation of hASBT and suggest that rapid modulation of its expression on the plasma membrane may contribute to the therapeutic effects of glucocorticoids in the treatment of bile acid malabsorption associated with intestinal inflammation. (Supported by Dept of Veteran Affairs and NIDDK).
AGA Abstracts
131 Cytomegalovirus (CMV) Induces Nf-κB in Monocytes/Macrophages: Mechanism for CMV Exacerbation of Inflammatory Bowel Disease (IBD) Phillip D. Smith, Masako Shimamura, Lois Musgrove, Lea Novak, Ronald H. Clements, William J. Britt, Lesley E. Smythies Background: Intestinal macrophages are profoundly non-inflammatory, likely due to stromal TGF-β down-regulation of pro-inflammatory, but not host defense, function of blood monocytes newly recruited to normal mucosa (JCI 115:66 '05; J Leuk Biol 80:492 '06). Despite the inability of intestinal macrophages to produce pro-inflammatory cytokines, the mucosa in CMV disease is intensely inflamed, and CMV-infected mucosal macrophages produce
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Na, n=3, p<0.01). Na-dependent adenosine uptake was significantly diminished during chronic enteritis (5.2 ± 0.5 pmol/ug protein in normal, 2.6 ± 0.2 in inflamed, n=3, p<0.01). RTQ-PCR analysis demonstrated that CNT2 mRNA expression was decreased during chronic intestinal inflammation (1.8 ± 0.1 fold, n=3, p<0.01). Methypredisolone (MP) treatment of rabbit with chronic enteritis alleviated the inhibition of Na-dependent adenosine uptake (4.7 ± 0.4 pmol/ug protein, n=3, p<0.01) and CNT2 mRNA expression (1 ± 0.1 fold, n= 3, p<0.01). Conclusions: Na-dependent adenosine uptake is mediated by CNT2 in intestinal villus cells but not crypt cells. Adenosine uptake and CNT2 mRNA expression were significantly inhibited in villus cells during chronic intestinal inflammation. MP reversed the inhibition of adenosine uptake and CNT2 mRNA expression in villus cells during chronic enteritis. These data indicate that inhibition of CNT2 mRNA expression and adenosine absorption in villus cells during chronic intestinal inflammation can be restored by steroid treatment.
129 The Crohn's Disease Candidate Gene Protein Tyrosine Phosphatase N2 (PTPN2) Is Activated By Gamma Interferon (IFNγ) in Intestinal Epithelial Cells (IECs) in An Adenosine-Monophosphate Kinase (Ampk) Dependent Manner Michael Scharl, Kim E. Barrett, Declan F. McCole Background: PTPN2 has recently been identified as a Crohn's disease (CD) candidate gene. This phosphatase dephosphorylates and inactivates proinflammatory modulators, such as the Signal Transducer and Activator of Transcription 1 (STAT1). IFNγ plays a major role in chronic inflammatory processes, such as CD, and many of its effects are mediated by STAT1. Therefore, PTPN2 could pivotally regulate inflammatory processes in the intestine. The cellular energy sensor, AMPK, has been shown to activate PTPN2 in human fibroblasts. Here, we investigate the role of PTPN2 in a model of intestinal inflammation using T84 intestinal epithelial cells. Methods: Protein analysis was performed by Western blot and RNA analysis by RT-PCR. PTPN2 activity was assessed by a fluorescent phosphatase assay and subcellular PTPN2 distribution by confocal microscopy. PTPN2 knock down was induced by siRNA. Results: Expression of PTPN2 mRNA was increased by IFNγ treatment of T84 monolayers (1000 U/ml), (p<0.01, n=3, 24-72h). Furthermore, IFNγ increased cytoplasmic (p<0.01, n=4, 48-72h) and nuclear (p<0.01, n=4, 24h) levels of PTPN2 protein as well as cytoplasmic PTPN2 phosphatase activity (p<0.05, n=4, 72h). IFNγ also altered the subcellular distribution of PTPN2, causing a cytoplasmic accumulation, that was prominent at 72h. Phosphorylation of STAT1 was reduced in parallel to the increase in PTPN2 activity (p<0.001, n=4, 24h vs. 72h). siRNA mediated knock-down of PTPN2 significantly enhanced IFNγinduced STAT1 phosphorylation (p<0.001, n=3, 24h). IFNγ increased AMPK activity as assessed by its phosphorylation (p<0.01, n=3, 6h). Inhibition of AMPK with Compound C (50 µM) decreased cytoplasmic (p<0.05, n=4, 72h) and nuclear (p<0.05, n=4, 72h) PTPN2 levels, and increased STAT1 phosphorylation in response to IFNγ (p<0.001, n=4, 24h). Cytoplasmic accumulation of PTPN2 was likewise impaired. However, AMPK activation with AICA-riboside-5'-phosphate (1 mM) affected neither PTPN2 expression nor STAT1 phosphorylation. Conclusion: Thus, the expression and activity of the CD candidate gene PTPN2 is increased by IFNγ. This occurs, at least in part, through AMPK, although AMPK alone is not sufficient for the response. Activated PTPN2 in turn reduces STAT1-mediated proinflammatory signal transduction in IECs. These data demonstrate a novel role for AMPKdependent activation of PTPN2 in the downregulation of proinflammatory signalling in a cellular model of intestinal inflammation. These findings support the hypothesis, that dysfunction of PTPN2 contributes to chronic inflammatory processes in the intestine, such as CD. Supported by the Crohn's and Colitis Foundation of America and NIH.
127 Bile Acids Decrease Ileal Mucin During Development of Experimental Necrotizing Enterocolitis Charity A. Reynolds, Ludmila Khailova, Bohuslav Dvorak, Kelly M. Arganbright, Melissa Halpern Background: Bile acids (BAs) facilitate digestion and transport of fats and sterols in the intestine and liver. However, accumulation of BAs in the intestine can result in damage to the intestinal epithelium. Using the neonatal rat model of necrotizing enterocolitis (NEC), we have previously shown that BAs accumulate in both the ileal lumen and enterocytes and these increased BA levels are positively correlated with disease severity. Importantly, when BAs are not allowed to accumulate, neonatal rat pups develop significantly less disease. Intestinal mucins protect the epithelial surface by forming a semi-permeable mucous layer between the lumen and the intestinal epithelium. In premature infants, a deficiency in the mucous layer has been suggested to contribute to intestinal injury during NEC. Muc2, the predominant secretory mucin produced by intestinal goblet cells, has been shown to be altered by BAs and transport of BAs via mucin is a critical step in normal fat absorption. Objective: To determine if BAs affect mucin production during the development of experimental NEC. Methods: Newborn Sprague-Dawley rats were divided into the following groups: DF (n=12), pups allowed to feed from the mother for 4 days and exposed to asphyxia and cold stress; NEC (n=12), pups hand-fed with formula for 4 days and exposed to asphyxia and cold stress, NEC + Chol (n=12); pups hand-fed with formula for 4 days, asphyxia and cold stressed and given 120 mg/kg/day cholestyramine to eliminate ileal BA; BA Gav (n= 5), newborn rats gavaged with 20mM Na deoxycholic acid twice per day for 2 days and Control (n=5), newborn rats gavaged with vehicle only. Muc2 positive cells were enumerated after immunohistological staining by counting positive cells per 100 intestinal epithelial cells. Results: Animals in the NEC group (median ileal damage score 2.5; NEC incidence 70%) had significantly lower numbers of Muc2+ cells than DF littermates (median damage score 0, NEC incidence 0%). In the NEC+Chol group (median damage score 1.5; NEC incidence 20%, p ≤ 0.01 vs NEC), where luminal BAs were prevented from accumulating, numbers of Muc2+ cells were signficantly increased compared to the NEC group. When exogenous BAs were introduced into the GI tract (BA Gav), numbers of Muc2+ cells were significantly reduced compared to animals given vehicle alone (Control). Conclusions: Increased ileal BAs result in decreased mucin production in neonatal rat intestine. Fewer Muc2+ cells may decrease transport of BAs independent of changes in active transport mechanisms, contributing to BA accumulation in the intestine and subsequent ileal barrier dysfunction.
130 Activated Innate Immune System in Irritable Bowel Syndrome? Jost Langhorst, Angela Junge, Andreas Rueffer, Jan Wehkamp, Dirk Foell, Andreas Michalsen, Frauke Musial, Gustav J. Dobos Background: Human defensins appear to be part of the innate immune system. Human βdefensin-2 (HBD-2) was the first inducible human anti-microbial protein discovered. It can be induced by probiotic microorganisms and pro-inflammatory cytokines. Recent results suggest, that HBD-2 is expressed in active intestinal inflammation, especially in ulcerative colitis (UC). Our aim was to evaluate fecal measurements of HBD-2 in patients with UC as well as irritable bowel syndrome (IBS) and healthy controls (HC). We expected that fecal HBD-2 levels would only be elevated in UC due to its inflammatory pathophysiology. Methods: Fecal specimens were collected from a total of 100 participants (30 with active UC, 47 IBS and 23 HC). Exclusion criterion was the current use of probiotics. Furthermore, IBS patients with elevated CRP or leukocytes, a history of bacterial overgrowth or infectious gastrointestinal disease over the last 6 month were excluded. Disease status was addressed in all participating subjects by medical history and current symptoms. In addition, each IBS and UC patient underwent ileocolonoscopy with histopathology. Fecal inflammation markers Lactoferrin (LF) and Calprotectin (Cal) were measured by ELISA and reported as µg/g. Fecal HBD-2 was measured by ELISA and reported as ng/g feces. Paraffin-embedded tissue from colonic biopsies was tested for HBD-2 peptides by immunohistochemistry. Results: LF as well as Cal was elevated in active UC (Mean: 152.1 ± S.E. 374.7 µg/g; 103.5 ± 87.1 µg/g), compared to IBS (8.4 ± 0.5 µg/g; 18.7 ± 23.1 µg/g), and healthy controls (0.4 ± 0.5 µg/g; 6.6 ± 5.0 µg/g). Scheffe post hoc tests revealed significant differences (p = 0.006) between active UC vs. IBS and HC. To the contrary, HBD-2 levels were highest in active UC (Mean: 106.9 ± S.E. 91.5 ng/g), almost as high in IBS (pts 74.9 ± 58.9 ng/g), and lowest for healthy controls (31.0 ± 15.4 ng/g). Scheffe post hoc tests revealed significant differences (p = 0.001) between the groups of patients (UC and IBS) vs. healthy controls. Immunohistochemical investigation was consistent with fecal secretion data and demonstrated the presence of βdefensin-2 peptides in colonic epithelial enterocytes in UC as well as IBS patients with elevated fecal HBD-2. Conclusions: The results imply, to the contrary to our hypothesis, that fecal levels of HBD-2 were significantly elevated in patients with IBS compared to healthy controls and similar to those in UC patients. The results suggest an activation of the mucosal innate defence system towards a proinflammatory response in IBS patients in the absence of macroscopic signs of inflammation.
128 Acute Regulation of Apical Sodium-Dependent Bile Acid Transporter (ASBT) By Dexamethasone in Human Intestinal Epithelial Cells Pradeep Kumar, Fadi Annaba, Seema Saksena, Pradeep K. Dudeja, Krishnamurthy Ramaswamy, Ravinder K. Gill, Waddah A. Alrefai Ileal apical ASBT mediates intestinal absorption of bile acids and is subject to extensive regulation. ASBT expression has been shown to be up-regulated by various stimuli such as glucocorticoids via transcriptional mechanisms. However, little is known about acute modulation of ASBT in the human intestine. Recent studies have shown that some of the biological effects of glucocorticoids occur in a transcription-independent manner. Therefore, the current studies were designed to examine the short-term effect of dexamethasone on ASBT activity and membrane protein expression. Human intestinal Caco2 cells were transiently cotransfected by electroporation (Amaxa) with expression vectors for human hASBT-V5 fusion protein and human glucocorticoid receptor (GR). The activity of ASBT was assessed by the measurement of Na+-dependent 3H-tuarocholic acid uptake. hASBT-V5 expression on apical membrane was determined by cell surface biotinylation. GR activation by dexamethasone significantly increased hASBT activity in a dose- and time-dependent manner. The maximum induction (an increase by 86.83 ± 18.9 % of control) occurred at 2 h incubation with 1 microM concentration of dexamethasone. This effect was completely abrogated in the presence of 0.5 microM of GR antagonist, RU-486 confirming the involvement of GR. Dexamethasoneinduced increase in ASBT activity appears to be mediated via activation of PI3 kinasedependent pathways since it was blocked in the presence of PI3 kinase inhibitors LY294002 (50 microM) and Wortmanin (5 microM). Parallel to the stimulation in its activity, the level of ASBT-V5 fusion protein expression on apical membrane of Caco2 cells was significantly increased (~ 60%) by dexamethasone. Conclusion: Our data show that dexamethsoneinduced stimulation of hASBT activity occurs via the activation of GR and PI3k-dependent pathways and is associated with an increase in its protein level on the membrane. Our studies provide new insights into short-term regulation of hASBT and suggest that rapid modulation of its expression on the plasma membrane may contribute to the therapeutic effects of glucocorticoids in the treatment of bile acid malabsorption associated with intestinal inflammation. (Supported by Dept of Veteran Affairs and NIDDK).
AGA Abstracts
131 Cytomegalovirus (CMV) Induces Nf-κB in Monocytes/Macrophages: Mechanism for CMV Exacerbation of Inflammatory Bowel Disease (IBD) Phillip D. Smith, Masako Shimamura, Lois Musgrove, Lea Novak, Ronald H. Clements, William J. Britt, Lesley E. Smythies Background: Intestinal macrophages are profoundly non-inflammatory, likely due to stromal TGF-β down-regulation of pro-inflammatory, but not host defense, function of blood monocytes newly recruited to normal mucosa (JCI 115:66 '05; J Leuk Biol 80:492 '06). Despite the inability of intestinal macrophages to produce pro-inflammatory cytokines, the mucosa in CMV disease is intensely inflamed, and CMV-infected mucosal macrophages produce
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