Open AccessRole of NLRP3 and CARD8 in the regulation of TNF-α induced IL-1β release in vascular smooth muscle cells
Author(s) -
Tebeng Nixon Tangi,
Ali Ateia Elmabsout,
Torbjörn Bengtsson,
Allan Sirsjö,
Karin Fransén
Publication year - 2012
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2012.1026
Subject(s) - inflammasome , gene silencing , gene knockdown , transfection , tumor necrosis factor alpha , oncogene , messenger rna , interleukin , vascular smooth muscle , apoptosis , biology , microbiology and biotechnology , cancer research , gene expression , gene , smooth muscle , inflammation , cytokine , endocrinology , cell cycle , immunology , biochemistry
Interleukin (IL)-1β is known to be activated by the inflammasome. Inflammasomeactivities depend on a plethora of moieties including NLRP3 and CARD8, which havebeen reported to be associated with several inflammatory diseases. Aortic smoothmuscle cells (AOSMCs) were transfected with siRNA targeting the NLRP3 and CARD8genes, followed by tumor necrosis factor-α (TNF-α) treatment. We found that TNF-αinduces IL-1β, IL-1Ra and NLRP3 genes but not CARD8. Silencing of the NLRP3 genesignificantly decreased IL-1β expression and release, the IL-1Ra expression showeda borderline non-significant increment, while CARD8 knockdown did not affect theIL-1β and IL-1Ra mRNA expression or IL-1β protein release. Our results suggestthat mainly NLRP3 plays a role in the regulation of IL-1β expression and releasein AOSMC and could be a potential future target for the treatment of atherosclerosisand other inflammatory diseases.