Manzo, B.A.; Bajaj-Elliott, M.; Atherton, J.; Thomas, R.; Sanderson, I.R.; Wilson, J.W.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA8
Academic Journal
H pylori can induce both apoptosis and proliferation of gastric epithelial cells. The balance between these two processes during bacterial infection depends on both host and microbial determinants and underlay the risk of developing cancer. Inhibitor of differentiation (Id/DNA binding) helix-loop-helix proteins are critically related to cell cycle progression, differentiation, and apoptosis. These effects are mediated by inhibiting the DNA binding of basic HLH transcription factors, such as the ubiquitous E47 and tissue-specific factors like myoD. We hypothesised that H pylori could regulate Id expression in gastric epithelial cells following infection. AGS cells (from a poorly differentiated gastric adenocarcinoma) were co-cuhured with H pylori 60190 wild type strain (1×108 bacteria/cell) from 2 to 48 hours. RT-PCR analysis revealed down-regulation for Id-1 and Id-3 mRNA levels, which occurred over the first 6 hours of exposure to H pylori. In contrast, Id-2 mRNA levels remained constant. In agreement with transcriptional data, Western blot analysis showed that protein levels were strongly and rapidly downregulated by the bacteria; again Id-2 protein levels were unaltered. Culture of AGS cells in presence of H pylori resulted in the accumulation of cells in the G1 phase of the cell cycle (69% after 24 hours compared with 48% in control cultures), as assessed by FACS analysis. No significant apoptosis was observed. In conclusion, H pylori results in decreased Id-1 and Id-3 expression in AGS cells in vitro, which is associated with arrest of the cells in G1 phase of the cell cycle. These results indicate that H pylori can alter the expression of key regulatory transcription factors controlling gene expression in the cell cycle.


Related Articles

  • C/EBP homologous protein inhibits tissue repair in response to gut injury and is inversely regulated with chronic inflammation. Waldschmitt, N; Berger, E; Rath, E; Sartor, R B; Weigmann, B; Heikenwalder, M; Gerhard, M; Janssen, K-P; Haller, D // Mucosal Immunology (1933-0219);Nov2014, Vol. 7 Issue 6, p1452 

    Loss of intestinal epithelial cell (IEC) homeostasis and apoptosis negatively affect intestinal barrier function. Uncontrolled activation of the unfolded protein response (UPR) in IEC contributes to an impaired barrier and is implicated in the pathogenesis of inflammatory bowel diseases....

  • STIMULATION OF MATRIX METALLOPROTEINASE-7 (MMP-7) BY HELICOBACTER PYLORI IN GASTRIC EPITHELIAL CELLS: ROLE IN EPITHELIAL CELL MIGRATION. Varro, A.; Wroblewski, L.E.; Pagliocca, A.; Pritchard, D.M.; Noble, P.-J.M.; Hart, C.A. // Gut;Apr2003 Supplement 1, Vol. 52, pA53 

    Background and Aims: Epithelial cell responses to bacterial infection include induction of MMP-7. We have examined the cellular mechanisms of H pylori stimulation of MMP-7 in gastric cells, and the consequences for gastric epithelial cell migration. Methods: Gastric biopses of H pylori positive...

  • PI-3-kinase is an essential anti-apoptotic effector in the proliferative response of primary human epithelial cells to mutant RAS. Gire, Véronique; Marshall, Christopher; Wynford-Thomas, David // Oncogene;5/4/2000, Vol. 19 Issue 19, p2269 

    In contrast to its growth-inhibitory effect on primary mesenchymal cells, RAS oncogene activation induces a proliferative phenotype in normal human thyroid epithelial cells in vitro, consistent with its putative role in tumour initiation. Using this model, we previously showed that activation of...

  • Apoptosis and JNK activation are differentially regulated by Fas expression level in renal tubular epithelial cells. Khan, Shenaz; Koepke, Alexandra; Jarad, George; Schlessman, Katie; Cleveland, Ronald P.; Wang, Bingcheng; Konieczkowski, Martha; Schelling, Jeffrey R. // Kidney International;Jul2001, Vol. 60 Issue 1, p65 

    Apoptosis and JNK activation are differentially regulated by Fas expression level in renal tubular epithelial cells. Background. In chronic renal disease, renal tubular epithelial cell (RTC) Fas expression is up-regulated, leading to apoptotic RTC deletion and tubular atrophy. In vitro,...

  • Inhibition of lens epithelial cell growth by induction of apoptosis: potential for prevention of posterior capsule opacification. Geissler, Francis T.; Li, David Wan-Cheng; James, Eric R.; Geissler, F T; Li, D W; James, E R // Journal of Ocular Pharmacology & Therapeutics;Dec2001, Vol. 17 Issue 6, p587 

    As a model of the cell proliferation occurring in posterior capsule opacification (PCO), lens epithelial cells (LEC) from human and rabbit capsulotomies, and a rabbit LEC line (N/N1003A) were grown in Dulbecco's Minimal Essential Media (MEM) with 10% fetal calf serum. LEC were exposed to the...

  • Intracellular Zinc Depletion Induces Caspase Activation and p21[sup Waf1/Cip1] Cleavage in Human... Chai, F.; Truong-Tran, A.Q.; Evdokiou, A.; Young, G.P.; Zalewski, P.D. // Journal of Infectious Diseases;9/15/2000 Supplement 1, Vol. 182, pS85 

    Examines the impact of zinc chelator (TPEN)-induced intracellular zinc depletion on apoptosis-linked events in some human malignant epithelial cell lines to better understand the mechanisms behind zinc deficiency-induced epithelial cell death. Apoptosis in zinc-depleted cells proceeding via a...

  • Up-regulation of production of TGF-β and IL-4 and down-regulation of IL-6 by apoptotic human bronchial epithelial cells. Hodge, Sandra; Hodge, Greg; Flower, Robert; Reynolds, Paul N; Scicchitano, Raffaele; Holmes, Mark // Immunology & Cell Biology;Dec2002, Vol. 80 Issue 6, p537 

    Summary Human bronchial epithelial cells secrete cytokines that play a role in immune responses in the lung. However, the roles of these cytokines in regulating epithelial repair following acute lung injury are largely unknown. Responses to injury include hyperplasia of epithelial cells and...

  • Induction of apoptosis before shedding of human intestinal epithelial cells. Grossmann, Johannes; Walther, Kathrin; Artinger, Monika; Rümmele, Petra; Woenckhaus, Matthias; Schölmerich, Jürgen // American Journal of Gastroenterology;Jun2002, Vol. 97 Issue 6, p1421 

    OBJECTIVES:Human intestinal epithelial cells (IECs) derive from stem cells at the crypt base and migrate along the so-called crypt-villus axis toward the intestinal lumen. As they reach the luminal surface in the colon or the villus tip in the small intestine, IECs are shed and their life cycle...

  • Mechanism of Clostridium difficile Toxin A-Induced Apoptosis in T84 Cells. Brito, Gerly A.C.; Fujji, Jun; Carneiro-Filho, Benedito A.; Lima, Aldo A.M.; Obrig, Tom; Guerrant, Richard L. // Journal of Infectious Diseases;11/15/2002, Vol. 186 Issue 10, p1438 

    This study is an investigation into the mechanism of Clostridium difficile toxin A-induced apoptosis in human intestinal epithelial cells. Toxin A induced apoptosis of T84 cells in a dose- and time-dependent fashion. Toxin A-induced apoptosis was completely inhibited by blocking toxin enzymatic...


Read the Article


Sign out of this library

Other Topics