scholarly journals Interferon-γ Augments CARD4/NOD1 Gene and Protein Expression through Interferon Regulatory Factor-1 in Intestinal Epithelial Cells

2003 ◽  
Vol 278 (35) ◽  
pp. 32962-32968 ◽  
Author(s):  
Tadakazu Hisamatsu ◽  
Manabu Suzuki ◽  
Daniel K. Podolsky
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Intestinal Epithelial Cells ◽  
Interferon Γ ◽  
Interferon Regulatory Factor ◽  
Intestinal Epithelial ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 1 ◽  
Gene And Protein Expression

scholarly journals Interferon-γ inhibits sirtuin 6 gene expression in intestinal epithelial cells through a microRNA-92b-dependent mechanism

2020 ◽  
Vol 318 (4) ◽  
pp. C732-C739
Author(s):  
Fangyi Liu ◽  
Xiao Wang ◽  
Hua Geng ◽  
Heng-Fu Bu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Intestinal Epithelial Cells ◽  
Specific Inhibitor ◽  
In Silico Analysis ◽  
Interferon Γ ◽  
Luciferase Assay ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
Intestinal Epithelial

Sirtuin 6 (Sirt6) is predominantly expressed in epithelial cells in intestinal crypts. It plays an important role in protecting intestinal epithelial cells against inflammatory injury. Previously, we found that colitis is associated with the downregulation of Sirt6 protein in the intestines. Here, we report that murine interferon-γ (Ifnγ) inhibits Sirt6 protein but not mRNA expression in young adult mouse colonocytes (YAMC, a mouse colonic epithelial cell line) in a dose- and time-dependent manner. Using microRNA array analysis, we showed that Ifnγ induces expression of miR-92b in YAMC cells. With in silico analysis, we found that the Sirt6 3′-untranslated region (UTR) contains a putative binding site for miR-92b. Luciferase assay showed that Ifnγ inhibited Sirt6 3′-UTR activity and this effect was mimicked by miR-92b via directly targeting the miR-92b seed site in the 3′-UTR of Sirt6 mRNA. Furthermore, Western blot demonstrated that miR-92b downregulated Sirt6 protein expression in YAMC cells. Blocking miR-92b with a specific inhibitor attenuated the inhibitory effect of Ifnγ on Sirt6 protein expression in the cells. Collectively, our data suggest that Ifnγ inhibits Sirt6 protein expression in intestinal epithelial cells via a miR-92b-mediated mechanism. miR-92b may be a novel therapeutic target for rescuing Sirt6 protein levels in intestinal epithelial cells, thereby protecting against intestinal mucosal injury caused by inflammation.

Interferon regulatory factor-2 (IRF-2) positively regulates the gene expression of Il-7 in intestinal epithelial cells

2003 ◽  
Vol 124 (4) ◽  
pp. A157
Author(s):  
Shigeru Oshima ◽  
Tetsuya Nakamura ◽  
Shin Namiki ◽  
Ki-Ichiro Tsuchiya ◽  
Ryuichi Okamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Interferon Regulatory Factor ◽  
Intestinal Epithelial ◽  
Regulatory Factor

scholarly journals DOP87 SUCNR1 a novel key protagonist in fistula development

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S126-S126
Author(s):  
C Bauset ◽  
L Gisbert-Ferrandiz ◽  
D Ortiz-Masia ◽  
S Coll ◽  
C Mamie ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Mrna Expression ◽  
Intestinal Epithelial Cells ◽  
Fistula Formation ◽  
Fistula Tract ◽  
Intestinal Epithelial ◽  
Gene And Protein Expression ◽  
Emt Markers ◽  
E Cadherin

Abstract Background Intestinal fistula is a common complication in CD patients whose aetiology is still not well-characterised. It is associated with an exacerbated inflammation and epithelial-to-mesenchymal transition (EMT), a process which allows a switch from epithelial towards a fibrotic behaviour. We have recently reported that SUCNR1 mediates intestinal inflammation and fibrosis1 but its role in fistula has not yet been analysed. Therefore, we aim to analyse the role of SUCNR1 in EMT and in fistula formation. Methods Intestinal resections were obtained from CD and non-IBD patients. Fistula specimens were identified by the surgeons and collected from B3-CD patients. The expression of SUCNR1 and EMT markers was analysed by qPCR and the protein expression of SUCNR1 by immunohistochemistry. HT-29 cells were treated with succinate (0,0.1,0.5,1,5 mM) or TGF-β (5 ng/ml) during 48 h and transfected with SUCNR1 siRNA. Expression of EMT markers was analysed by qPCR and western blot. Intestinal fibrosis was induced in vivo using the heterotopic transplant model in WT and Sucnr1−/− mice and expression of EMT markers was analysed by qPCR and by confocal microscopy. Statistical analysis was performed with one-way ANOVA followed by Newman–Keuls test. Correlations were analysed with the Spearman’s coefficient. Results In intestinal resections from B3-CD patients, SUCNR1 mRNA expression was significantly increased when compared with B2-CD or non-IBD controls and it correlates positively with the mRNA expression of Snail1 and Snail2 and negatively with that of E-Cadherin. In the fistula tract, SUCNR1 is expressed in intestinal epithelial cells and lamina propria cells of the submucosa with a higher intensity in cells close to the fistula tract than in more distant areas. Succinate induced, in a dose–response manner, a significant increase in Vimentin, Snail1 and Snail2 expression and a reduction in E-cadherin expression. This effect was completely abolished when SUCNR1 was transiently knocked-down. WT-grafts 7 days after surgery exhibited: (a) an increase in gene and protein expression of SUCNR1, (b) an increase in the expression of Vimentin, Snail1 and Snail2 and a significant reduction in E-Cadherin compared with WT-grafts at day 0. Of interest, KO-grafts at day 7 failed to exhibited changes in the expression of Vimentin, Snail1, Snail2 or E-Cadherin. Conclusion SUCNR1 is increased specifically in the fistula tract of B3-CD patients. It mediates EMT in intestinal epithelial cells and in a murine model of fibrosis. Hence, SUCNR1 might be a potential pharmacological target for fistula treatment. Reference

Co-operation of interleukin-17 and interferon-γ on chemokine secretion in human fetal intestinal epithelial cells

2001 ◽  
Vol 120 (5) ◽  
pp. A189
Author(s):  
Hiroki Takaya ◽  
Akira Andoh ◽  
Jin Makino ◽  
Takashi Okuno ◽  
Kazunori Hata ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Intestinal Epithelial

Chromatin bound by survivin regulates the glycolytic switch in interferon-γ producing CD4+ T cells

2021 ◽  
Author(s):  
Malin Erlandsson ◽  
Karin Andersson ◽  
Nina Oparina ◽  
Venkataragavan Chandrasekaran ◽  
Anastasios Damdimopoulos ◽  
...  
Keyword(s):  
T Cells ◽  
Glucose Utilization ◽  
Interferon Γ ◽  
Interferon Regulatory Factor ◽  
Metabolic Adaptation ◽  
Regulatory Factor ◽  
Cell Functions ◽  
Interferon Regulatory Factor 1 ◽  
Direct Binding ◽  
Nuclear Survivin

Abstract Upon activation, CD4+ T cells adapt metabolically to fulfill their effector function in autoimmunity. Here we show that nuclear survivin is essential for transcriptional regulation of glucose utilization. We found that the glycolytic switch in interferon (IFN) g–producing CD4+ cells is dependent on a complex of survivin with interferon regulatory factor 1 (IRF1), and Smad3 and was reversed by survivin inhibition. Transcriptome analysis of CD4+ cells and sequencing of survivin-bound chromatin identified a hub of metabolism regulating genes whose transcription depended on survivin. Direct binding of survivin to IRF1 and SMAD3 promoted IRF1-mediated transcription, repressed SMAD3 activity, and lowered PFKFB3 production. Inhibiting survivin upregulated PFKFB3, restored glycolysis, and reduced glucose uptake, improving control over IFNg-dependent T-cell functions. Thus, IRF1-survivin-SMAD3 interactions are important for metabolic adaptation of CD4+ cells and provide an attractive strategy to counteract IFNg-dependent inflammation.

LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway

2003 ◽  
Vol 284 (5) ◽  
pp. G821-G829 ◽  
Author(s):  
Wenlin Deng ◽  
De-An Wang ◽  
Elvira Gosmanova ◽  
Leonard R. Johnson ◽  
Gabor Tigyi
Keyword(s):  
Epithelial Cells ◽  
Cytochrome C ◽  
Protein Expression ◽  
Caspase 3 ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
Antiapoptotic Activity

We previously showed ( Gastroenterology 123: 206–216, 2002) that lysophosphatidic acid (LPA) protects and rescues rat intestinal epithelial cells (IEC-6) from apoptosis. Here, we provide evidence for the LPA-elicited inhibition of the mitochondrial apoptotic pathway leading to attenuation of caspase-3 activation. Pretreatment of IEC-6 cells with LPA inhibited campothecin-induced caspase-9 and caspase-3 activation and DNA fragmentation. A caspase-9 inhibitor peptide mimicked the LPA-elicited antiapoptotic activity. LPA elicited ERK1/ERK2 and PKB/Akt phosphorylation. The LPA-elicited antiapoptotic activity and inhibition of caspase-9 activity were abrogated by pertussis toxin, PD 98059, wortmannin, and LY 294002. LPA reduced cytochrome c release from mitochondria and prevented activation of caspase-9. LPA prevented translocation of Bax from cytosol to mitochondria and increased the expression of the antiapoptotic Bcl-2 mRNA and protein. LPA had no effect on Bcl-xl, Bad, and Bak mRNA or protein expression. These data indicate that LPA protects IEC-6 cells from camptothecin-induced apoptosis through Gi-coupled inhibition of caspase-3 activation mediated by the attenuation of caspase-9 activation due to diminished cytochrome c release, involving upregulation of Bcl-2 protein expression and prevention of Bax translocation.

Decrease of glutaminase expression by interferon-γ in human intestinal epithelial cells

1994 ◽  
Vol 1 (5) ◽  
pp. 428-435 ◽  
Author(s):  
Peter Sarantos ◽  
Zaher Abouhamze ◽  
Edward M. Copeland ◽  
Wiley W. Souba
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Interferon Γ ◽  
Intestinal Epithelial ◽  
Human Intestinal Epithelial Cells
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