Neonicotinoid pesticides disrupt gingival epithelial barrier function

Neonicotinoid pesticides are highly persistent in the environment, with detection in periodontal blood reported. Although an association with gingival inflammation has been shown, the mechanism related to periodontal disease remains unclear. Previous study found that coxsackievirus and adenovirus receptor (CXADR) is involved in gingival tissue epithelial barrier function, thus the effects of neonicotinoids on CXADR were examined. High performance liquid chromatography of salivary samples from 16 volunteers detected acetamiprid, clothianidin, imidacloprid, and thiamethoxam. Administration of neonicotinoids (Σneonicotinoids) resulted in loss of cell-surface CXADR, which was restored by bafilomycin A1, a lysosomal inhibitor. Using a three-dimensional tissue model of human gingival epithelial cells, Σneonicotinoids were found to increase permeability to lipopolysaccharide (LPS) and peptidoglycan (PGN), which was dependent on CXADR. It is thus suggested that neonicotinoids cause mislocalization of CXADR into lysosomes, leading to gingival barrier function disruption, which allows for bacterial virulence factors to penetrate subepithelial tissues.