Specialized Pro-Resolving Lipid Mediators Distinctly Modulate Silver Nanoparticle-Induced Pulmonary Inflammation in...

Area of Science:

• Environmental Health
• Immunology
• Toxicology

Background:

• Metabolic syndrome (MetS) increases susceptibility to environmental inhalation exposures, like particulate air pollution.
• Mechanisms linking MetS to exacerbated pulmonary inflammation from nanoparticle exposure are unclear.
• Previous studies showed MetS mice exhibit increased pulmonary inflammation after silver nanoparticle (AgNP) exposure, linked to reduced specialized pro-resolving mediators (SPMs).

Purpose of the Study:

• To investigate if administering specific SPMs (resolvin E1, protectin D1, maresin) post-AgNP exposure can modulate inflammatory responses in healthy and MetS mouse models.
• To determine the differential effects of these SPMs on pulmonary inflammation and toxicity.
• To explore SPMs as potential therapeutic strategies for mitigating particulate-induced lung inflammation in susceptible individuals.

Main Methods:

• Healthy and MetS mouse models were exposed to silver nanoparticles (AgNPs) or a vehicle control via oropharyngeal aspiration.
• Mice received treatments of resolvin E1 (RvE1), protectin D1 (PD1), or maresin (MaR1), or a vehicle control, 24 hours post-exposure.
• Pulmonary inflammation and toxicity endpoints were assessed three days after AgNP exposure.

Main Results:

• MetS mice exposed to AgNPs and treated with vehicle showed significantly exacerbated pulmonary inflammation compared to healthy mice.
• RvE1 treatment reduced neutrophil infiltration in both healthy and MetS mice, decreasing exacerbated levels in MetS models and lowering proinflammatory cytokines.
• PD1 reduced exacerbated neutrophilia in MetS mice, associated with decreased proinflammatory cytokines and increased IL-10.
• MaR1 treatment reduced AgNP-induced neutrophil influx in both models, decreasing proinflammatory cytokines and increasing IL-10, particularly in MetS mice.

Conclusions:

• Specific SPMs, including RvE1, PD1, and MaR1, can differentially regulate inflammatory responses to AgNP exposure.
• SPM treatment, especially MaR1, shows promise in reducing pulmonary inflammation and may benefit individuals with MetS or other conditions predisposing them to environmental exposures.
• Targeting SPMs could be a viable therapeutic strategy for managing inflammatory conditions triggered by inhaled particulates.