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-?B, which "primes" cells for inflammasome activation by inducing the expression of NLRP3 or AIM2 receptor and pro-IL-1?, 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-1?. 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-?B 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.

SUBMITTER: Panchanathan R 

PROVIDER: S-EPMC5053719 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature