Ultraviolet Radiation‐Induced Downregulation of SERCA2 Mediates Activation of NLRP3 Inflammasome in Basal Cell Carcinoma1. (6th March 2017)

• Record Type: Journal Article
• Authors: Ahmad, Israr; Muneer, Kashiff M.; Chang, Michelle E.; Nasr, Hana M.; Clay, Jacqueline M.; Huang, Conway C.; Yusuf, Nabiha
• Is Part Of: Photochemistry and photobiology. Volume 93:Number 4(2017)
• Page Start: 1025
• Page End: 1033
• Publication Date: 2017-03-06
• Subjects: Photochemistry -- Periodicals; Light -- Physiological effect -- Periodicals; 541.35
• DOI: 10.1111/php.12725
• Languages: English
• ISSNs: 0031-8655

Abstract

Abstract: 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 Ca 2+ mobilization in activation of the NLRP3 inflammasome by UVB exposure using HaCaT keratinocytes. We have demonstrated that UVB exposure blocks Ca 2+ mobilization by downregulating the expression of sarco/endoplasmic reticulum Ca 2+ ‐ATPase (SERCA2), a component of store‐operated Ca 2+ entry that leads to activation of the NLRP3 inflammasome. Abstract : Critical role for Ca 2+ mobilization in activation of the nucleotide‐binding domain, leucine‐rich‐repeat‐containing family, pyrin domain‐containing 3 (NLRP3) inflammasome. Ultraviolet (UV) B exposure blocks Ca 2+ mobilization by downregulating the expression of sarco/endoplasmic reticulum Ca 2+ ‐ATPase (SERCA2), a component of store‐operated Ca 2+ entry (SOCE) that leads to activation of the NLRP3 inflammasome.