Investigating the Molecular Mechanisms Underlying Early Response to Inflammation and Helicobacter pylori Infection in Human Gastric Epithelial Cells
Articolo
Data di Pubblicazione:
2023
Citazione:
Investigating the Molecular Mechanisms Underlying Early Response to Inflammation and Helicobacter pylori Infection in Human Gastric Epithelial Cells / G. Martinelli, M. Fumagalli, S. Piazza, N. Maranta, F. Genova, P. Sperandeo, E. Sangiovanni, A. Polissi, M. Dell'Agli, E. De Fabiani. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 24:20(2023 Oct 13), pp. 15147.1-15147.23. [10.3390/ijms242015147]
Abstract:
Helicobacter pylori is a leading cause of chronic gastric inflammation, generally associated with gastritis and adenocarcinoma. Activation of the NF-κB pathway mainly contributes to the inflammatory phenotype observed in H. pylori infection in humans and experimental models. Since the gastric epithelium undergoes rapid turnover, inflammation and pathogenicity of H. pylori result from early phase and chronically activated pathways. In the present study we investigated the early host response to H. pylori in non-tumoral human gastric epithelial cells (GES-1). To dissect the pathogen-specific mechanisms we also examined the response to tumor necrosis factor (TNF), a prototypical cytokine. By analyzing the activation state of NF-κB signaling, cytokine expression and secretion, and the transcriptome, we found that the inflammatory response of GES-1 cells to H. pylori and TNF results from activation of multiple pathways and transcription factors, e.g., NF-κB and CCAAT/enhancer-binding proteins (CEBPs). By comparing the transcriptomic profiles, we found that H. pylori infection induces a less potent inflammatory response than TNF but affects gene transcription to a greater extent by specifically inducing transcription factors such as CEBPβ and numerous zinc finger proteins. Our study provides insights on the cellular pathways modulated by H. pylori in non-tumoral human gastric cells unveiling new potential targets.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
AGS cells; CEBPβ; GES-1 cells; Helicobacter pylori; IL-6; IL-8; NF-κB
Elenco autori:
G. Martinelli, M. Fumagalli, S. Piazza, N. Maranta, F. Genova, P. Sperandeo, E. Sangiovanni, A. Polissi, M. Dell'Agli, E. De Fabiani
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