Neonicotinoid pesticides disrupt gingival epithelial barrier function

Area of Science:

• Environmental Science
• Toxicology
• Periodontology

Background:

• Neonicotinoid pesticides are environmentally persistent and detected in human blood.
• Their association with gingival inflammation is known, but the mechanism of periodontal disease involvement is unclear.
• Coxsackievirus and adenovirus receptor (CXADR) is crucial for gingival epithelial barrier function.

Purpose of the Study:

• To investigate the effects of neonicotinoids on CXADR and gingival epithelial barrier function.
• To elucidate the mechanism by which neonicotinoids may contribute to periodontal disease.

Main Methods:

• Salivary samples from 16 volunteers were analyzed for neonicotinoid presence using high-performance liquid chromatography.
• Neonicotinoids were administered to a 3D human gingival epithelial cell model.
• Cell-surface CXADR levels and epithelial permeability to LPS and PGN were assessed.
• The effect of bafilomycin A1 (a lysosomal inhibitor) on CXADR localization was examined.

Main Results:

• Four neonicotinoids (acetamiprid, clothianidin, imidacloprid, thiamethoxam) were detected in volunteer saliva.
• Neonicotinoid exposure led to the loss of cell-surface CXADR.
• This loss was reversible with bafilomycin A1, indicating lysosomal involvement.
• Neonicotinoids increased epithelial permeability to LPS and PGN in a CXADR-dependent manner.

Conclusions:

• Neonicotinoids cause the mislocalization of CXADR into lysosomes, disrupting gingival epithelial barrier function.
• This disruption allows bacterial virulence factors to penetrate subepithelial tissues, suggesting a role in periodontal disease.
• Neonicotinoid exposure poses a risk to periodontal health through barrier disruption.