OBJECTIVE: Involvement of non-canonical inflammasome, comprising inflammatory human caspase-4, caspase-5, and Gasdermin D, in the pathogenesis of oral lichen planus (OLP) has never been demonstrated. We aimed to determine human caspase-4, caspase-5, and Gasdermin D expressions in OLP, to correlate their expressions with OLP severity, and to measure salivary interleukin (IL)-1β levels. STUDY DESIGN: OLP and normal oral mucosal specimens (n = 42 each) were processed for immunohistochemistry or immunoblotting. The clinical score for OLP severity was assessed at the most severe site. The immunohistochemical (IHC) score was a summation of intensity and positive cell scores. Salivary IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Median IHC scores of caspase-4 and Gasdermin D in OLP group were significantly greater than those in normal mucosal group (P <
.01), consistent with significantly upregulated expressions by immunoblotting (P <
.05). The IHC scores of caspase-4 and Gasdermin D were positively correlated with the clinical scores (P <
.05). Salivary IL-1β levels in the OLP group were significantly greater than those in the normal mucosal group (P <
.001). CONCLUSIONS: Our study demonstrates enhanced human caspase-4 and Gasdermin D expressions in relation to increased OLP severity with elevated salivary IL-1β levels, proposing clinical applications of these biomolecules as potential prognostic markers and/or new therapeutic intervention for OLP.