Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", University of Milan, 20133 Milan, Italy.
Int J Mol Sci. 2023 Oct 13;24(20):15147. doi: 10.3390/ijms242015147.
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 infection in humans and experimental models. Since the gastric epithelium undergoes rapid turnover, inflammation and pathogenicity of result from early phase and chronically activated pathways. In the present study we investigated the early host response to 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 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 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 in non-tumoral human gastric cells unveiling new potential targets.
是慢性胃炎症的主要原因，通常与胃炎和腺癌有关。NF-κB 途径的激活主要导致人类和实验模型中观察到的 感染的炎症表型。由于胃上皮细胞经历快速更新， 的炎症和致病性源自早期和慢性激活的途径。在本研究中，我们研究了非肿瘤性人类胃上皮细胞 (GES-1) 中对 的早期宿主反应。为了剖析病原体特异性机制，我们还检查了对肿瘤坏死因子 (TNF) 的反应，TNF 是一种典型的细胞因子。通过分析 NF-κB 信号转导、细胞因子表达和分泌以及转录组的激活状态，我们发现 GES-1 细胞对 和 TNF 的炎症反应源自多种途径和转录因子的激活，例如 NF-κB 和 CCAAT/增强子结合蛋白 (CEBPs)。通过比较转录组谱，我们发现与 TNF 相比， 感染诱导的炎症反应较弱，但通过特异性诱导转录因子（如 CEBPβ 和许多锌指蛋白）对基因转录的影响更大。我们的研究提供了对非肿瘤性人类胃细胞中 调节的细胞途径的深入了解，揭示了新的潜在靶点。
