Alterations in plasma membrane ion channel structures stimulate NLRP3 inflammasome activation in APOL1 risk milieu.

ABSTRACT: We evaluated alterations in the structural configurations of channels and activation of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome formation in apolipoprotein L1 (APOL1) risk and nonrisk milieus. APOL1G1- and APOL1G2-expressing podocytes (PD) displayed enhanced K⁺ efflux, induction of pyroptosis, and escalated transcription of interleukin (IL)-1β and IL-18. APOL1G1- and APOL1G2-expressing PD promoted the transcription as well as translation of proteins involved in the formation of inflammasomes. Since glyburide (a specific inhibitor of K⁺ efflux channels) inhibited the transcription of NLRP3, IL-1β, and IL-18, the role of K⁺ efflux in the activation of inflammasomes in APOL1 risk milieu was impl

SUBMITTER: Jha A 

PROVIDER: S-EPMC7298666 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature