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Kinnunen K, Piippo N, Loukovaara S, et al. Lysosomal destabilization activates the NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs). J Cell Commun Signal. 2017;11(3):275-279doi: 10.1007/s12079-017-0396-4.
Kinnunen, K., Piippo, N., Loukovaara, S., Hytti, M., Kaarniranta, K., & Kauppinen, A. (2017). Lysosomal destabilization activates the NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs). Journal of cell communication and signaling, 11(3), 275-279. https://doi.org/10.1007/s12079-017-0396-4
Kinnunen, K, et al. "Lysosomal destabilization activates the NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs)." Journal of cell communication and signaling vol. 11,3 (2017): 275-279. doi: https://doi.org/10.1007/s12079-017-0396-4
Kinnunen K, Piippo N, Loukovaara S, Hytti M, Kaarniranta K, Kauppinen A. Lysosomal destabilization activates the NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs). J Cell Commun Signal. 2017 Sep;11(3):275-279. doi: 10.1007/s12079-017-0396-4. Epub 2017 May 25. PMID: 28547650; PMCID: PMC5559399.
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J Cell Commun Signal. 2017 Sep;11(3):275-279. doi: 10.1007/s12079-017-0396-4. Epub 2017 May 25.

Lysosomal destabilization activates the NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs).

Journal of cell communication and signaling

K Kinnunen, N Piippo, S Loukovaara, M Hytti, K Kaarniranta, A Kauppinen

Affiliations

  1. Department of Ophthalmology, Kuopio University Hospital, P.O. Box 100, FI-70029, Kuopio, Finland. [email protected].
  2. Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland. [email protected].
  3. Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
  4. School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.
  5. Unit of Vitreoretinal Surgery, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, FI-00029, Helsinki, Finland.
  6. Department of Ophthalmology, Kuopio University Hospital, P.O. Box 100, FI-70029, Kuopio, Finland.

PMID: 28547650 PMCID: PMC5559399 DOI: 10.1007/s12079-017-0396-4

Abstract

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.

Keywords: Angiogenesis; Atherosclerosis; Diabetic retinopathy; Inflammasome; Inflammation

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