p120-catenin downregulation selectively modulates inflammatory susceptibility in eyelid specimens of rosacea.

Previous investigations have implicated the p120-catenin (p120) system in the regulation of cutaneous inflammation. This prospective observational study was performed to evaluate adherens junction and tight junction protein expression in eyelid specimens of rosacea. Lysates were made from elective repair of involutional ectropion tissue. Western blotting (WB) was performed on tissue from 16 patients with rosacea and 16 control eyelid specimens and immunohistochemical (IHC) staining was performed on specimens from 12 patients with rosacea and 12 control eyelids to evaluate the presence of p120, β-catenin, E-cadherin, afadin, claudin-1, and zonula occludens-1 (ZO-1). The intensity of junctional and cytoplasmic staining on the epithelium was scored 1-4 by two blinded investigators and percentage of p120 positively-staining nuclei were counted across five consecutive 40x fields. WB expression was determined by band densitometry. On WB, levels of p120 were significantly decreased in rosacea patients compared with controls (median = 0.19 vs. 0.72, p = 0.01). On IHC, there was no significant difference in junctional staining intensity scores between rosacea and control patients. However, p120 nuclear localization was reduced in rosacea patients by 16% (p = 0.0001).These results suggest that nuclear p120 is downregulated in eyelid specimens of rosacea, while other key junctional proteins appear unaffected. While these findings are consistent with p120's role in inflammatory signaling with previously implicated proteins in rosacea and suggest that this downregulation facilitates the pathogenesis of rosacea through signal transduction effects without overt disruption of epithelial junction integrity, additional study may clarify the role of p120 in its pathogenesis.