Human umbilical cord-derived mesenchymal stem cells attenate histaminergic effect of intestinal mucosa through bax/bcl-2 pathway in food allergic enteritis

This study was designed to comprehensively elucidate the mechanism by which human umbilical cord-derived mesenchymal stem cell (hUC-MSC) therapy modulates epithelial cell apoptosis and preserves the integrity of the intestinal barrier. A series of meticulously planned in vivo and in vitro experiments were conducted to evaluate the effects of hUC-MSC treatment on various pathological parameters. Our in vivo findings demonstrated that hUC-MSC therapy significantly attenuated pathological damage, as evidenced by decreased tissue necrosis and inflammation. Furthermore, ultrastructural injury to the intestinal epithelium and mast cell infiltration were notably alleviated. With respect to the systemic immune response, serum levels of key immune factors, including IgG, IgE, mouse mast cell protease (mMCP-1), histamine, interleukin (IL)-6, and tumor necrosis factor (TNF)-α, were observably reduced following hUC-MSC treatment. At the molecular level, in jejunal tissue from food allergy mice treated with hUC-MSCs, the expression of IL-6 and TNF-α mRNA was downregulated, whereas the expression of , interferon (IFN)-γ, T-box transcription factor (T-bet) mRNA was upregulated. In vitro experiments using histamine-induced apoptosis in FHs 74 Int cells revealed that hUC-MSC therapy led to a marked decrease in the expression levels of pro-apoptotic proteins Bax, caspase-3, and cleaved caspase-3. Concurrently, significant upregulation of both the anti-apoptotic protein Bcl-2 and tight junction protein Zonula Occludens-1 (ZO-1) was observed. hUC-MSCs substantially improved cellular viability during histamine challenge by suppressing apoptosis (quantified by Annexin V/7-AAD staining) and reducing reactive oxygen species (ROS) generation in FHs 74 Int cells, demonstrating dual cytoprotective effects against histamine-induced toxicity. Our findings provide compelling evidence that hUC-MSCs mediate anti-apoptotic effects via modulation of the Bax/Bcl-2 pathway in histamine-stimulated intestinal mucosa during allergic responses. These results reveal novel therapeutic potential for hUC-MSCs in maintaining epithelial homeostasis and intestinal barrier function in food allergy-associated enteritis, suggesting promising clinical applications for this disorder.