α-Terpineol Attenuates PS-NP-Induced Lung Injury in Association with NF-κB Signaling and GSDMD-Related Pyroptosis
Year: 2026
Type: article
Abstract: Emerging environmental contaminants called polystyrene nanoplastics (PS-NPs) may be harmful to respiratory health. With a focus on inflammatory responses, NF-κB signaling, and GSDMD-mediated pyroptosis, this work examined the impact of α-terpineol (α-TPN), a naturally occurring monoterpene with antioxidant and anti-inflammatory qualities, on PS-NP-induced lung damage. A549 cells were initially used to assess the effects of PS-NPs and α-TPN. CCK-8, LDH release, and Annexin V/PI flow cytometry were used to measure cell viability, cellular damage, and cell death, respectively. ELISA was used to measure the levels of IL-1β, IL-6, and IL-8, while NF-κB signaling and pyroptosis-related proteins were examined by Western blotting and immunofluorescence. The protective effects of α-TPN on lung function and lung pathology were then assessed using a mouse model of PS-NP-induced lung injury. IL-1β, IL-6, and TNF-α levels in bronchoalveolar lavage fluid were measured to evaluate inflammatory responses. NF-κB signaling, NLRP3/ASC inflammasome-associated proteins, and GSDMD-related pyroptosis were further evaluated in lung tissues using Western blotting, immunohistochemistry, and immunofluorescence. PS-NP exposure increased LDH release, Annexin V-positive cell death, and IL-1β, IL-6, and IL-8 levels in A549 cells. These effects were associated with enhanced NF-κB p65 signaling and changes in the expression of pyroptosis-related proteins, including NLRP3, ASC, cleaved caspase-1, and GSDMD-N. α-TPN pretreatment attenuated cellular injury and inflammatory responses and partially reversed these protein changes. In mice, PS-NP exposure impaired pulmonary function, characterized by increased enhanced pause (Penh) and decreased expiratory flow at 50% expired volume (EF50), minute ventilation (MV), and respiratory frequency (fbpm). Alveolar wall thickening, edema, inflammatory cell infiltration, and structural damage were also brought on by PS-NP exposure, and bronchoalveolar lavage fluid (BALF) showed increased levels of TNF-α, IL-1β, and IL-6. Treatment with α-TPN decreased BALF inflammatory cytokine levels and enhanced lung histology and pulmonary function. Additionally, α-TPN decreased GSDMD-N, cleaved caspase-1, mature IL-18, and mature IL-1β levels in lung tissues and inhibited changes in NF-κB-related proteins, indicating that its protective effects may entail modulation of GSDMD-related pyroptosis and NF-κB-associated inflammatory signaling.α-TPN alleviates PS-NP-induced lung injury and inflammatory responses, potentially by regulating inflammation and pyroptosis. These results imply that α-TPN could be a natural active substance for reducing lung damage caused by PS-NPs.
Institution: Kunming Medical University
Language: English
Subfield: Pollution
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7225630867