title: Hypoxia primes human normal prostate epithelial cells and cancer cell lines for the NLRP3 and AIM2 inflammasome activation.
abstract: The molecular mechanisms by which hypoxia contributes to prostatic chronic inflammation (PCI) remain largely unknown. Because hypoxia stimulates the transcriptional activity of NF-κB, which "primes" cells for inflammasome activation by inducing the expression of NLRP3 or AIM2 receptor and pro-IL-1β, we investigated whether hypoxia could activate the NLRP3 and AIM2 inflammasome in human normal prostate epithelial cells (PrECs) and cancer cell lines. Here we report that hypoxia (1% O2) treatment of PrECs, prostate cell lines, and a macrophage cell line (THP-1) increased the levels of NLRP3, AIM2, and pro-IL-1β. Further, hypoxia in cells potentiated activation of the NLRP3 and AIM2 inflammasome activity. Notably, hypoxia "primed" cells for NLRP3 and AIM2 inflammasome activation through stimulation of the NF-κB activity. Our observations support the idea that hypoxia in human prostatic tumors contributes to PCI, in part, by priming cells for the activation of NLRP3 and AIM2 inflammasome.
authors.affiliation: Cincinnati VA Medical Center, Cincinnati, OH 45220, USA.|Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Panchanathan
authors.affiliation: Cincinnati VA Medical Center, Cincinnati, OH 45220, USA.|Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Cincinnati VA Medical Center, Cincinnati, OH 45220, USA.|Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Divaker
authors.initials: D
authors.lastname: Choubey
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D011472:Prostatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology
chemical_list: C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
keywords: cancer; hypoxia; inflammasome; inflammation; prostate