Role of NLRP3 and CARD8 in the regulation of TNF-α induced IL-1β release             in vascular smooth muscle cells.
Interleukin (IL)-1β is known to be activated by the inflammasome. Inflammasome             activities depend on a plethora of moieties including NLRP3 and CARD8, which have             been reported to be associated with several inflammatory diseases. Aortic smooth             muscle cells (AOSMCs) were transfected with siRNA targeting the NLRP3 and CARD8             genes, followed by tumor necrosis factor-α (TNF-α) treatment. We found that TNF-α             induces IL-1β, IL-1Ra and NLRP3 genes but not CARD8. Silencing of the NLRP3 gene             significantly decreased IL-1β expression and release, the IL-1Ra expression showed             a borderline non-significant increment, while CARD8 knockdown did not affect the             IL-1β and IL-1Ra mRNA expression or IL-1β protein release. Our results suggest             that mainly NLRP3 plays a role in the regulation of IL-1β expression and release             in AOSMC and could be a potential future target for the treatment of atherosclerosis             and other inflammatory diseases.
Department of Clinical Medicine, School of Health and Medical                     Science, Örebro University, Örebro, Sweden.
Tebeng Nixon
TN
Tangi
Ali Ateia
AA
Elmabsout
Torbjörn
T
Bengtsson
Allan
A
Sirsjö
Karin
K
Fransén
D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha