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Helicobacter pylori-induced chronic gastritis represents a well-established risk factor for gastric cancer (GC). However, the mechanism by which chronic inflammation caused by H. pylori induces the development of GC is unclear. H. pylori can influence host cell signalling pathways to induce gastric disease development and mediate cancer promotion and progression. Toll-like receptors (TLRs), as pattern recognition receptors (PRRs), play a key role in the gastrointestinal innate immune response, and their signalling has been implicated in the pathogenesis of an increasing number of inflammation-associated cancers. The core adapter myeloid differentiation factor-88 (MyD88) is shared by most TLRs and functions primarily in H. pylori-triggered innate immune signalling. MyD88 is envisioned as a potential target for the regulation of immune responses and is involved in the regulation of tumourigenesis in a variety of cancer models. In recent years, the TLR/MyD88 signalling pathway has received increasing attention for its role in regulating innate and adaptive immune responses, inducing inflammatory activation and promoting tumour formation. In addition, TLR/MyD88 signalling can manipulate the expression of infiltrating immune cells and various cytokines in the tumour microenvironment (TME). In this review, we discuss the pathogenetic regulatory mechanisms of the TLR/MyD88 signalling cascade pathway and its downstream molecules in H. pylori infection-induced-associated GC. The focus is to elucidate the immunomolecular mechanisms of pathogen recognition and innate immune system activation of H. pylori in the TME of inflammation-associated GC. Ultimately, this study will provide insight into the mechanism of H. pylori-induced chronic inflammation-induced GC development and provide thoughts for GC prevention and treatment strategies. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Citation

Meiqi Liu, Zhizhong Hu, Chengkun Wang, Yang Zhang. The TLR/MyD88 signalling cascade in inflammation and gastric cancer: the immune regulatory network of Helicobacter pylori. Journal of molecular medicine (Berlin, Germany). 2023 Jul;101(7):767-781

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PMID: 37195446

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