Exposure to diesel exhaust (DE) induces thyroid injury characterized primarily by follicular destruction accompanied by elevated expression of proinflammatory cytokines. To assess the effects of DE exposure on thyroid inflammatory injury and investigate potential interventional pathways, we established an inhalation exposure mouse model and an aryl hydrocarbon receptor (AHR) inhibitor intervention model. We found that DE exposure induced significant injury to the thyroid tissues of mice, characterized by follicular rupture and colloid extravasation. Western blotting analyses revealed a significant upregulation of AHR expression following DE exposure. Immunofluorescence assays demonstrated that DE exposure activated the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. In addition, the expression levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were significantly increased following DE exposure. Our inhibitor intervention model confirmed the critical role of AHR in mediating DE-induced thyroid inflammatory injury. Compared with the DE-exposed group, inhibition of AHR activity significantly ameliorated the thyroid tissue structure in mice, and thyroid hormone levels showed no significant difference from those of the control group. This mechanism may be mediated via the AHR-NLRP3 signaling pathway, which was further validated by our in vitro intervention model. Collectively, this study provides a novel strategy for the prevention of DE-induced thyroid inflammatory injury, and our experimental evidence lays a solid foundation for further investigating the role of AHR in inflammatory processes. • DE exposure induces thyroid inflammatory injury in mice. • DE mediates thyroid inflammatory injury by activating the AHR-NLRP3 signaling pathway. • Targeted inhibition of AHR effectively attenuates DE-induced thyroid inflammatory injury.
Hao et al. (Wed,) studied this question.