DEPTOR alleviates LPS-induced inflammation and ER stress in WI-38 cells
Main Article Content
Keywords
endoplasmic reticulum stress, DEPTOR, inflammation, LPS, WI-38 cells
Abstract
Background: Pediatric pneumonia is a severe inflammatory condition frequently precipitated by bacterial endotoxins, such as lipopolysaccharide (LPS), which can elicit oxidative stress, endoplasmic reticulum (ER) stress, and apoptotic cell death. DEP domain-containing mTOR-interacting protein (DEPTOR), an endogenous inhibitor of mTOR signaling, has been implicated in the regulation of inflammation and ER homeostasis. However, its specific function in the pathogenesis of pneumonia remains poorly defined.
Methods: WI-38 human fetal lung fibroblast cells were employed to establish an in vitro model of LPS-induced inflammation. DEPTOR was overexpressed via plasmid transfection to examine its functional role. The impact of DEPTOR on pro-inflammatory cytokine release, oxidative and ER stress responses, apoptosis, and nuclear factor kappa B signaling was comprehensively evaluated using quantitative real-time polymerase chain reaction, Western blot analysis, enzyme-linked-immunosorbent serologic assay, flow cytometry, and biochemical assays.
Results: DEPTOR expression is significantly downregulated in LPS-stimulated WI-38 cells (P < 0.01). DEPTOR overexpression markedly suppresses LPS-induced pro-inflammatory cytokine production (P < 0.01), ameliorates oxidative and ER stress—as indicated by decreased lipid peroxidation and restoration of superoxide dismutase and glutathione levels (P < 0.01)—and inhibits apoptosis, reducing apoptotic cell percentages by over 10% (P < 0.01).
Conclusion: These results suggest that DEPTOR confers a protective role against LPS-induced cellular injury, supporting its potential as a promising therapeutic target for mitigating
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