5-aminolevulinic acid photodynamic therapy (ALA-PDT) is highly effective in the treatment of condyloma acuminata (CA). Previous research has indicated that ALA-PDT could induce cell death by different mechanisms, including apoptosis and autophagy, but the role of pyroptosis in ALA-PDT remains uncertain. Thus, this study aimed to explore whether pyroptosis is a potential mechanism of ALA-PDT killing human papillomavirus (HPV) infected cells. HPV-positive HeLa cells were exposed to ALA-PDT, then cell viability assay, lactate dehydrogenase release (LDH) assay, detection of reactive oxygen species (ROS), quantitative real-time PCR (qPCR), and western blot were used to evaluate pyroptosis induced by ALA-PDT. Results suggested that ALA-PDT enhanced the expression of NLRP3, caspase-1, GSDMD, and the production of inflammatory cytokines such as IL-1β and IL-18. In addition, ALA-PDT induced the production of ROS and led to the destruction of the cell membrane. The inhibition of pyroptosis reduced the killing of HeLa cells by ALA-PDT. This study demonstrates that ALA-PDT induces pyroptosis in HPV-positive cells, which provides some explanation for the mechanism of ALA-PDT to treat CA and HPV infection-related diseases.
