Objective: To investigate the role of Helicobacter pylori (HP) on the regulation of NF-κB/ IL-17 signaling, mechanisms underlying apoptosis in human megakaryocyte cell lines Dami. Methods: Firstly, the mouse model of immune thrombocytopenia (ITP) was established. Then, the mice were subjected to gastric perfusion with HP. Next, the changes in platelet and bone marrow megakaryocyte classification were assessed in each group. Human megakar- yocyte Dami cells were treated with HP in vitro for 3, 6, or 9 h; and the rates of apoptosis in each group were then evaluated with flow cytometry. Fluorescent quantitative PCR and Western blotting were implemented for assessing the expression of Bcl-2 and Bax, which are related to apoptosis, and p65, which is associated with the NF-κB pathway. The expression of these proteins was also evaluated after treatment with PDTC, an inhibitor of the NF-κB pathway inhibitor. Results: In vivo, exogenous administration of HP was found to increase the optical density value for the anti-HP antibody in HP-infected BALB/c mice. Meanwhile, the platelet counts in the HP-infected ITP mice model were significantly reduced compared with non-infected ITP mice. In vitro, the apoptotic rate of Dami cells increased gradually with the prolongation of the exposure to HP; the most noticeable change was at 6 h, and there was a significant difference between 0 h and 6 h. The expression of Bax, p-p65, and IL-17 also increased progressively with the prolongation HP exposure, while the expression of anti-apoptotic Bcl- 2 protein decreased gradually, especially at 6 h, and the expression of total p65 did not change significantly compared with baseline. Anecdotally, these effects were reversed by the application of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB signaling. Conclusion: HP can promote platelet destruction in ITP mice, and the underlying mechan- isms may be related to accelerating apoptosis of megakaryocytes by the activation of the NF- κB/IL-17 pathway.
CITATION STYLE
Lei, H., Ma, Y., Tan, J., & Liu, Q. (2021). Helicobacter pylori regulates the apoptosis of human megakaryocyte cells via NF-κB/IL-17 signaling. OncoTargets and Therapy, 14, 2065–2074. https://doi.org/10.2147/OTT.S268056
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