Peluso, Silvia (2009) Epigenetic dynamics of Helicobacter pylori-induced COX-2 activation. [Tesi di dottorato] (Inedito)

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Epigenetic dynamics of Helicobacter pylori-induced COX-2 activation
Autori:
AutoreEmail
Peluso, Silviasilviaebasta@gmail.com
Data: 2009
Numero di pagine: 104
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Biologia e patologia cellullare e molecolare "L. Califano"
Scuola di dottorato: Medicina molecolare
Dottorato: Genetica e medicina molecolare
Ciclo di dottorato: 22
Coordinatore del Corso di dottorato:
nomeemail
Di Lauro, Robertodilauro@szn.it
Tutor:
nomeemail
Chiariotti, Lorenzochiariot@unina.it
Data: 2009
Numero di pagine: 104
Parole chiave: epigenetic, Helicobacter pylori, COX-2
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/07 - Microbiologia e microbiologia clinica
Area 06 - Scienze mediche > MED/04 - Patologia generale
Depositato il: 19 Mag 2010 13:36
Ultima modifica: 30 Apr 2014 19:38
URI: http://www.fedoa.unina.it/id/eprint/3820
DOI: 10.6092/UNINA/FEDOA/3820

Abstract

Background and Aims: Cyclooxigenase (COX)-2 is over expressed in gastrointestinal neoplasia and Helicobacter pylori (H. pylori) infection is casually linked to gastric cancer. We undertook this study to investigate the mechanism mediating H. pylori-induced COX-2 expression in human gastric epithelial cell line MKN28. Methods: MKN28 cells were infected with wild-type H. pylori 60190 strain for different time points, and the levels of COX-2 messenger RNA (mRNA) and protein expression were evaluated using real-time polymerase chain reaction (PCR) and Western blotting, respectively. Chromatin immunoprecipitation assays were performed to evaluate the level of histone modifications and the recruitment of histone deacetylases (HDACs) 1, and 2, nuclear transcription factor (NF-κB) and RNA polymerse II (PolII) to the COX-2 promoter. The technique of MALDI-TOF MS was used to determine the methylation analysis of CpG islands of the COX-2 promoter. Results: H. pylori induced a time-dependent increase of mRNA and protein expression of COX-2 in MKN28 cells. Furthermore, H. pylori-infected gastric epithelial cells showed dynamic changes of methylation and acetylation pattern of histone H3 at the promoter of COX-2 gene. Preventing histone deacetylation by the histone deacetylase inhibitor trichostatin A (TSA) augumented the H. pylori-induced COX-2 response. After exposure to H. pylori, we found a decreased in global histone deacetylase expression and activity. The hyperacetylation of histone H3 correlate with the release of HDAC 1, which first decreased and later reappeared at the COX-2 promoter. Moroever after H. pylori infection, NF-κB and RNA polymerase II were time-dependently recruited to the COX-2 promoter. In addition we show a dynamic changes in the methylaion status of promoter CpGs. Conclusions: These results show for the first time that H. pylori-induced activation of COX-2 gene transcription was caused by interference with epigenetic mechanisms regulating COX-2 gene accessibility. These patways may contribute to the host response in H. pylori-associated gastric inflammation and carcinogenesis.

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