Silica Nanoparticles Elicit Pulmonary Inflammation via STING-Dependent Activation of NF-κB p65 Signaling Pathway

Abstract

Silica nanoparticles (SiNPs) are common nanoparticles that are widely used in industrial and medical applications. Inhalation exposure to SiNPs is frequently inevitable in modern society. While the adverse effects of SiNPs on lung injury have been extensively documented, the intrinsic mechanisms underlying SiNPs-induced pulmonary inflammation remain incompletely understood. This study demonstrates that the stimulator of interferon genes (STING) plays an essential role in SiNPs-triggered lung inflammation. In vitro, SiNPs induced bone marrow derived macrophags (BMDMs) death and activated the STING pathway. Knockout the expression of STING alleviated SiNPs-induced inflammatory responses and subsequent cell death. Further mechanism investigations revealed that STING activation promotes nuclear translocation of NF-κB p65 and subsequent activation of the NF-κB pathway, ultimately driving the secretion of inflammatory factors. In vivo, SiNPs-induced NF-κB activation and inflammatory infiltration were significantly attenuated in STING-deficient (STING⁻/⁻) mice. These findings reveal that targeting the STING signaling pathway may represent a potential therapeutic strategy for mitigating lung inflammation caused by silica particles.