title: Ultraviolet Radiation-Induced Downregulation of SERCA2 Mediates Activation of NLRP3 Inflammasome in Basal Cell Carcinoma.
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 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.
authors.affiliation: Department of Dermatology, Skin Diseases Research Center, Birmingham, AL.
authors.forename: Israr
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: Department of Dermatology, Skin Diseases Research Center, Birmingham, AL.
authors.forename: Kashiff M
authors.initials: KM
authors.lastname: Muneer
authors.affiliation: Department of Dermatology, Skin Diseases Research Center, Birmingham, AL.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Chang
authors.affiliation: Department of Dermatology, Skin Diseases Research Center, Birmingham, AL.
authors.forename: Hana M
authors.initials: HM
authors.lastname: Nasr
authors.affiliation: Department of Dermatology, Skin Diseases Research Center, Birmingham, AL.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Clay
authors.affiliation: Department of Dermatology, Skin Diseases Research Center, Birmingham, AL.
authors.forename: Conway C
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Dermatology, Skin Diseases Research Center, Birmingham, AL.|Veteran Affairs Medical Center, Birmingham, AL.|Comprehensive Cancer Center, University of Alabama, Birmingham, AL.
authors.forename: Nabiha
authors.initials: N
authors.lastname: Yusuf
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D015536:Down-Regulation / Q000528:radiation effects*; D006706:Homeostasis; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism* / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014466:Ultraviolet Rays
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium