Vitamin D Attenuates Airway Inflammation via the Sema7A/Integrin-β1/NF-κB Axis in Asthma

Background: Glucocorticoid resistance in asthma is frequently associated with persistent airway inflammation and oxidative stress. Although vitamin D has been reported to exert anti-inflammatory effects and restore steroid sensitivity, the underlying signaling mechanisms remain unclear. Given that Semaphorin 7A (Sema7A) and its receptor Integrin-β1 are implicated in immune activation and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated inflammatory responses, this study aimed to elucidate how Vitamin D confers protection against bronchial inflammation and redox imbalance, emphasizing the potential regulatory role of the Sema7A/Integrin-β1/NF-κB axis. Methods: To model allergic airway disease, we utilized a murine asthma model induced by ovalbumin (OVA) and Lipopolysaccharide (LPS)-treated human bronchial epithelial (BEAS-2B) cells. Airway inflammation and oxidative stress were evaluated using enzyme-linked immunosorbent assay (ELISA), histopathological examination, and biochemical assays. In vitro cell proliferation, cytokine secretion, and reactive oxygen species (ROS) generation were measured. The expression of Sema7A, Integrin-β1, and NF-κB-related proteins was analyzed by Western blotting and reverse transcription quantitative PCR (RT-qPCR). Functional rescue assays were conducted by overexpressing Sema7A in BEAS-2B cells. Results: In the OVA-induced asthma mouse model, vitamin D treatment markedly reduced Th2 cytokines (IL-4, IL-5, IL-13; all p p p p p in vivo and in vitro systems, whereas Sema7A overexpression reactivated this pathway and partially diminished the anti-inflammatory effects of vitamin D. Conclusion: Vitamin D mitigates airway inflammation and oxidative stress in allergic asthma by suppressing the Sema7A/Integrin-β1/NF-κB signaling pathway. These findings reveal a novel mechanistic insight into the anti-inflammatory action of vitamin D and highlight its therapeutic potential in allergic airway diseases.