Leukemia Inhibitory Factor via JAK‐STAT Signaling Drives Beryllium Sulfate–Induced Epithelial–Mesenchymal Transition in 16HBE Cells

Beryllium and its compounds are classified as carcinogens, and prolonged exposure can trigger chronic beryllium disease. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is known to play a critical role in the development and progression of numerous diseases. Leukemia inhibitory factor (LIF), a key upstream cytokine of the JAK-STAT pathway, has been implicated in regulating inflammatory responses and epithelial-mesenchymal transition (EMT) in various diseases. However, the specific involvement of the JAK-STAT pathway and LIF in beryllium sulfate (BeSO₄)-induced EMT in human bronchial epithelial (16HBE) cells remains unclear. To investigate the regulatory mechanisms, we examined the effects of BeSO₄ on 16HBE cells and targeted the JAK-STAT pathway using both pharmacological inhibition (niclosamide) and genetic silencing of LIF. Subsequently, we assessed cell morphology, proliferative capacity, inflammatory protein levels, and EMT marker expression. Our findings demonstrated that BeSO₄ exposure inhibited 16HBE cell proliferation and activated the JAK-STAT pathway. Pretreatment with niclosamide significantly mitigated cellular inflammation and the EMT process induced by BeSO₄. Additionally, silencing LIF markedly reduced JAK-STAT pathway activation and decreased the expression of EMT markers. This study uncovers a novel mechanism underlying BeSO₄-induced EMT in 16HBE cells, providing valuable insights into the molecular mechanisms of toxicity induced by beryllium and its compounds.