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

• Published in: Photochemistry and photobiology Vol. 93; no. 4; pp. 1025 - 1033
• Main Authors: Ahmad, Israr, Muneer, Kashiff M., Chang, Michelle E., Nasr, Hana M., Clay, Jacqueline M., Huang, Conway C., Yusuf, Nabiha
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2017
• Subjects: Activation; Basal cell carcinoma; Ca2+-transporting ATPase; Calcium (reticular); Calcium - metabolism; Calcium influx; Calcium mobilization; Cancer; Carcinoma; Carcinoma, Basal Cell - metabolism; Carcinoma, Basal Cell - pathology; Caspase-1; Cell Line; Down-Regulation - radiation effects; Endoplasmic reticulum; Exposure; Homeostasis; Humans; Immune response; Incidence; Inflammasomes; Inflammasomes - metabolism; Innate immunity; Interleukin 1; Keratinocytes; Keratinocytes - metabolism; Keratinocytes - radiation effects; Leucine; Microorganisms; Neoplasms, Radiation-Induced - metabolism; Neoplasms, Radiation-Induced - pathology; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Pyrin protein; Radiation effects; Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism; Skin; Skin cancer; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Stimuli; Toxins; Ultraviolet radiation; Ultraviolet Rays
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.12725

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. Critical role for Ca2+ mobilization in activation of the nucleotide‐binding domain, leucine‐rich‐repeat‐containing family, pyrin domain‐containing 3 (NLRP3) inflammasome. Ultraviolet (UV) B exposure blocks Ca2+ mobilization by downregulating the expression of sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA2), a component of store‐operated Ca2+ entry (SOCE) that leads to activation of the NLRP3 inflammasome.