Endogenous immune defenses provide an intrinsic barrier against external entity invasion. Microplastics in the environment, especially those at the nanoscale (nanoplastics or NPs), may pose latent health risks through direct exposure. While links between nanoplastics and inflammatory processes have been established, detailed insights into how they may perturb the innate immune mechanisms remain uncharted. Employing murine and macrophage (RAW264.7) cellular models subjected to polystyrene nanoplastics (PS-NPs), our investigative approach encompassed an array of techniques: Cell Counting Kit-8 assays, flow cytometric analysis, acridine orange/ethidium bromide (AO/EB) fluorescence staining, cell transfection, cell cycle scrutiny, genetic manipulation, messenger RNA expression profiling via quantitative real-time PCR, and protein expression evaluation through western blotting. The results showed that PS-NPs caused RAW264.7 cell apoptosis, leading to cell cycle arrest, and activated the cGAS-STING pathway. This resulted in NF-κB signaling activation and increased pro-inflammatory mediator expression. Importantly, PS-NPs-induced activation of NF-κB and its downstream inflammatory cascade were markedly diminished after the silencing of the STING gene. Our findings highlight the critical role of the cGAS-STING pathway in the immunotoxic effects induced by PS-NPs. We outline a new mechanism whereby nanoplastics may trigger dysregulated innate immune and inflammatory responses via the cGAS/STING pathway.
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http://dx.doi.org/10.1016/j.ecoenv.2024.116255 | DOI Listing |
Mol Cancer
December 2024
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China.
cGAS-STING pathway stands at the forefront of innate immunity and plays a critical role in regulating adaptive immune responses, making it as a key orchestrator of anti-tumor immunity. Despite the great potential, clinical outcomes with cGAS-STING activators have been disappointing due to their unfavorable in vivo fate, signaling an urgent need for innovative solutions to bridge the gap in clinical translation. Recent advancements in nanotechnology have propelled cGAS-STING-targeting nanomedicines to the cutting-edge of cancer therapy, leveraging precise drug delivery systems and multifunctional platforms to achieve remarkable region-specific biodistribution and potent therapeutic efficacy.
View Article and Find Full Text PDFJ Adv Res
December 2024
Department of Pathology, Xuzhou Medical University, Xuzhou, China. Electronic address:
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a crucial mechanism in antiviral defense and innate immunity pathway. Ferroptosis, characterized by iron dependence and lipid peroxidation, represents a specialized form of cell death. A burgeoning collection of studies has demonstrated that the cGAS-STING signaling pathway participates in the homeostatic regulation of the organism by modulating ferroptosis-associated enzyme activity or gene expression.
View Article and Find Full Text PDFAlzheimers Res Ther
December 2024
Department of Neurology and Institute on Aging and Brain Disorders, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Lujiang Road 17, Hefei, 230001, China.
Background: Recent research has postulated that the activation of cGAS-STING-interferon signalling pathways could be implicated in the pathogenesis of Alzheimer's disease (AD). However, the precise types of interferons and related cytokines, both from the brain and periphery, responsible for cognitive impairment in patients with AD remain unclear.
Methods: A total of 131 participants (78 [59.
J Exp Clin Cancer Res
December 2024
Department of Oncology, Molecular Biotechnology Center "G. Tarone", University of Torino, Piazza Nizza 44, Torino, 10126, Italy.
Background: Malignant pleural mesothelioma (MPM) is a highly chemo-refractory and immune-evasive tumor that presents a median overall survival of 12-14 months when treated with chemotherapy and immunotherapy. New anti-tumor therapies as well as the concomitant reactivation of immune destruction are urgently needed to treat patients with this tumor. The aim of this work is to investigate the potential effect of ecteinascidin derivatives as lurbinectedin as new first-line treatment option in MPM, alone and in combination with immunotherapy.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Mitochondrial dysfunction is a key event in many pathological conditions, including neurodegenerative processes. When mitochondria are damaged, they release damage-associated molecular patterns (DAMPs) that activate mito-inflammation. The present study assessed mito-inflammation after in vitro oxygen-glucose deprivation as a representation of ischaemia, followed by reoxygenation (OGD/R) of HT22 cells and modulation of the inflammatory response by melatonin.
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