Ultraviolet Radiation‐Induced Downregulation of SERCA2 Mediates Activation of NLRP3 Inflammasome in Basal Cell Carcinoma

Basal cell carcinomas (BCCs) account for majority of skin malignancies in the United States. The incidence of BCCs is strongly associated with exposure of ultraviolet (UV) radiation. Nucleotide‐binding domain, leucine‐rich‐repeat‐containing family, pyrin domain‐containing 3 (NLRP3) inflammasome plays an important role in innate immune responses. Different stimuli such as toxins, microorganisms and particles released from injured cells activate the NLRP3 inflammasome. Activated NLRP3 results in activation of caspase‐1, which cleaves pro‐IL‐1β to active IL‐1β. In this study, we have shown that NLRP3 is expressed in human basal cell carcinomas. The proximal steps in activation of NLRP3 inflammasome are not well understood. Here, we have attempted to elucidate a critical role for Ca²⁺ mobilization in activation of the NLRP3 inflammasome by UVB exposure using HaCaT keratinocytes. We have demonstrated that UVB exposure blocks Ca²⁺ mobilization by downregulating the expression of sarco/endoplasmic reticulum Ca²⁺‐ATPase (SERCA2), a component of store‐operated Ca²⁺ entry that leads to activation of the NLRP3 inflammasome.