Taxamairin B inhibits inflammatory response by suppressing activation of PI3K/AKT/NF-kappaB signaling in a mouse model of transfusion-related acute lung injury.
BACKGROUND Transfusion-related acute lung injury (TRALI) is a serious adverse event of blood transfusion, characterized by pulmonary inflammation, edema, and neutrophil infiltration. This study aimed to explore the protective effects of taxamairin B (Taxa B), a natural component derived from Taxusmairei, on lung damage and inflammation in a mouse model of TRALI. METHODS A TRALI mouse model was established through sequential injection of lipopolysaccharide (LPS) and major histocompatibility complex (MHC) antibody. Extravascular lung water, extravascular plasma equivalents, lung weight/dry ratio, and protein concentration in bronchoalveolar lavage fluid (BALF) were measured. Histopathological changes were performed using hematoxylin-eosin staining. Neutrophil extracellular trap (NET) formation was evaluated by immunofluorescence staining. ELISA was conducted to quantify inflammatory cytokine levels in BALF and NET levels in mouse blood samples. Protein levels of PI3K, Akt, and NF-κB, as well as their phosphorylated levels, were measured by Western blotting. RESULTS Taxa B improved the survival of model mice by mitigating lung injury, reducing pulmonary edema, and attenuating lung tissue damage. Moreover, Taxa B suppressed NET formation in lung tissues and blood samples of model mice. Following TRALI induction, the levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) were significantly elevated while IL-10 levels were reduced, and these alterations were counteracted by Taxa B administration. Importantly, Taxa B inhibited the phosphorylated levels of PI3K, Akt, NF-κB, and IκBα in lung tissues of model mice. CONCLUSION Taxa exerts anti-inflammatory effects in a mouse model of TRALI by inhibiting the PI3K/Akt/NF-κB signaling.