Toll-like receptor 4 expression in the epithelium of inflammatory periapical lesions. An immunohistochemical study

Toll-like receptors (TLR) are essential for the innate immune response against invading pathogens and have been described in immunocompetent cells of areas affected by periapical disease. Besides initiating the inflammatory response, they also directly regu- late epithelial cell proliferation and survival in a variety of settings. This study evaluates the in situ expression of TLR4 in periapical granu- lomas (PG) and radicular cysts, focusing on the epithelial compartment. Twenty-one periapical cysts (PC) and 10 PG were analyzed; 7 dentigerous non-inflamed fol- licular cyst (DC) served as control. TLR4 expression was assessed by immunohisto- chemistry. TLR4 immunoreaction products were detected in the epithelium of all speci- mens, with a higher percentage of immunos- tained cells in PG. Although TLR4 overexpres- sion was detected in both PG and PC, there were differences that seemed to be related to the nature of the lesion, since in PG all epithe- lial cells of strands, islands and trabeculae were strongly immunoreactive for TLR4, whereas in PC only some areas of the basal and suprabasal epithelial layers were immunostained. This staining pattern is con- sistent with the action of TLR4: in PG it could promote formation of epithelial cell rests of Malassez and in epithelial strands and islands the enhancement of cell survival, proliferation and migration, whereas in PC TLR4 could pro- tect the lining epithelium from extensive apop-tosis. These findings go some way towards answering the intriguing question of why many epithelial strands or islands in PG and the lining epithelium of apical cysts regress after non surgical endodontic therapy, and suggest that TLR4 plays a key role in the patho- biology of the inflammatory process related to periapical disease.