Open AccessLysosomal destabilization activates the NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs)
Author(s) -
Kinnunen K.,
Piippo N.,
Loukovaara S.,
Hytti M.,
Kaarniranta K.,
Kauppinen A.
Publication year - 2017
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-017-0396-4
Subject(s) - inflammasome , pyrin domain , inflammation , umbilical vein , autocrine signalling , microbiology and biotechnology , receptor , caspase 1 , chemistry , medicine , immunology , biology , biochemistry , in vitro
Inflammation is a crucial component in the pathogenesis of many vascular diseases, such as atherosclerosis and diabetes. Inflammasomes are intracellular signalling complexes whose activation promotes inflammation. Nucleotide‐binding domain and Leucine‐rich repeat Receptor containing a Pyrin domain 3 (NLRP3) is a pattern recognition receptor (PRR) forming the best‐known inflammasome. Disturbances in NLRP3 have been associated with multiple diseases. The purpose of this study was to explore the lysosomal destabilization‐related NLRP3 inflammasome signaling pathway in human endothelial cells. In order to prime and activate NLRP3, human umbilical vein cells (HUVECs) were exposed to TNF‐α and the lysosomal destructive agent Leusine‐Leusine‐O‐Methylesther (Leu‐Leu‐OMe), respectively. A caspase‐1 inhibitor was used to block caspase‐1’s enzymatic function and an interleukin 1 receptor antagonist (IL‐1RA) to prevent any possible secondary effects of IL‐1β. Leu‐Leu‐OMe increased the expression of NLRP3, IL‐1β, and IL‐18 in HUVECs. Exposure to Leu‐Leu‐OMe significantly promoted the production of IL‐6 and IL‐8 in primed HUVECs; this effect was prevented by the pre‐treatment of cells with an IL‐1RA. Our results suggest that lysosomal destabilization activates the NLRP3 inflammasome pathway that promotes the production of IL‐6 and IL‐8 in an autocrine manner in HUVEC cells.