Nasal instillation of polystyrene nanoplastics induce lung injury via mitochondrial DNA release and activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-signaling cascade.

Nanoplastics (NPs) are a common type of degraded plastic material associated with adverse health effects such as pulmonary injury. However, the molecular mechanism(s) underlying lung injury as caused by NPs remains uncertain. Thus, we herein investigated the pulmonary toxicity of NPs on RAW264.7 cells and C57BL/6 mice. Our in vitro study indicated that NPs induced oxidative stress, cell death, inflammation, and the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-signaling pathway. Mice in our in vivo study displayed significant pulmonary fibrosis, inflammation, apoptosis, necrosis, and excessive double-stranded DNA release into serum and bronchoalveolar lavage fluid. Our mechanistic exploration uncovered cGAS-STING-signaling activation as the leading cause of NPs-induced pulmonary fibrosis. The current study opens an avenue toward elucidating the role of the cGAS-STING-signaling pathway in NPs-induced pulmonary injury.