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Crosstalk within the gastric epithelium, which is closely in contact with stromal fibroblasts in the gastric mucosa, has a pivotal impact in proliferation, differentiation and transformation of the gastric epithelium. The human pathogen Helicobacter pylori colonises the gastric epithelium and represents a risk factor for gastric pathophysiology. Infection of H. pylori induces the activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which is involved in the pro-inflammatory response but also in cell survival. In co-cultures with human gastric fibroblasts (HGF), we found that apoptotic cell death is reduced in the polarised human gastric cancer cell line NCI-N87 or in gastric mucosoids during H. pylori infection. Interestingly, suppression of apoptotic cell death in NCI-N87 cells involved an enhanced A20 expression regulated by NF-κB activity in response to H. pylori infection. Moreover, A20 acts as an important negative regulator of caspase-8 activity, which was suppressed in NCI-N87 cells during co-culture with gastric fibroblasts. Our results provide evidence for NF-κB-dependent regulation of apoptotic cell death in cellular crosstalk and highlight the protective role of gastric fibroblasts in gastric epithelial cell death during H. pylori infection.

Original publication

DOI

10.1016/j.bbamcr.2022.119364

Type

Journal article

Journal

Biochim Biophys Acta Mol Cell Res

Publication Date

12/2022

Volume

1869

Keywords

Caspase-8, Gastric cancer, Gastric mucosoids, Gastric organoids, NF-κB, Stromal fibroblasts, Caspase 8, Cell Survival, Coculture Techniques, Epithelial Cells, Fibroblasts, Helicobacter Infections, Helicobacter pylori, Humans, NF-kappa B, Transcription Factors