Native and oxidised lipoproteins negatively regulate the serum amyloid A‐induced NLRP3 inflammasome activation in human macrophages

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Nurmi , K , Niemi , K , Kareinen , I , Silventoinen , K , Lorey , M B , Chen , Y , Kouri , VP , Parantainen , J , Juutilainen , T , Öörni , K , Kovanen , P T , Nordström , D , Matikainen , S & Eklund , K K 2021 , ' Native and oxidised lipoproteins negatively regulate the serum amyloid A‐induced NLRP3 inflammasome activation in human macrophages ' , Clinical Translational Immunology , vol. 10 , 1323 . https://doi.org/10.1002/cti2.1323

Title: Native and oxidised lipoproteins negatively regulate the serum amyloid A‐induced NLRP3 inflammasome activation in human macrophages
Author: Nurmi, Katariina; Niemi, Katri; Kareinen, Ilona; Silventoinen, Kristiina; Lorey, Martina B; Chen, Yan; Kouri, Vesa‐Petteri; Parantainen, Jukka; Juutilainen, Timo; Öörni, Katariina; Kovanen, Petri T; Nordström, Dan; Matikainen, Sampsa; Eklund, Kari K
Contributor: University of Helsinki, HUS Internal Medicine and Rehabilitation
University of Helsinki, Department of Anatomy
University of Helsinki, Departments of Faculty of Veterinary Medicine
University of Helsinki, TRIMM - Translational Immunology Research Program
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Doctoral Programme in Biomedicine
University of Helsinki, HUS Musculoskeletal and Plastic Surgery
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Wihuri Research Institute
University of Helsinki, Clinicum
University of Helsinki, HUS Internal Medicine and Rehabilitation
University of Helsinki, Department of Medicine
Date: 2021
Language: eng
Number of pages: 20
Belongs to series: Clinical Translational Immunology
ISSN: 2050-0068
URI: http://hdl.handle.net/10138/334096
Abstract: Objectives The NLRP3 inflammasome plays a key role in arterial wall inflammation. In this study, we elucidated the role of serum lipoproteins in the regulation of NLRP3 inflammasome activation by serum amyloid A (SAA) and other inflammasome activators. Methods The effect of lipoproteins on the NLRP3 inflammasome activation was studied in primary human macrophages and THP-1 macrophages. The effect of oxidised low-density lipoprotein (LDL) was examined in an in vivo mouse model of SAA-induced peritoneal inflammation. Results Native and oxidised high-density lipoproteins (HDL3) and LDLs inhibited the interaction of SAA with TLR4. HDL3 and LDL inhibited the secretion of interleukin (IL)-1 beta and tumor necrosis factor by reducing their transcription. Oxidised forms of these lipoproteins reduced the secretion of mature IL-1 beta also by inhibiting the activation of NLRP3 inflammasome induced by SAA, ATP, nigericin and monosodium urate crystals. Specifically, oxidised LDL was found to inhibit the inflammasome complex formation. No cellular uptake of lipoproteins was required, nor intact lipoprotein particles for the inhibitory effect, as the lipid fraction of oxidised LDL was sufficient. The inhibition of NLRP3 inflammasome activation by oxidised LDL was partially dependent on autophagy. Finally, oxidised LDL inhibited the SAA-induced peritoneal inflammation and IL-1 beta secretion in vivo. Conclusions These findings reveal that both HDL3 and LDL inhibit the proinflammatory activity of SAA and this inhibition is further enhanced by lipoprotein oxidation. Thus, lipoproteins possess major anti-inflammatory functions that hinder the NLRP3 inflammasome-activating signals, particularly those exerted by SAA, which has important implications in the pathogenesis of cardiovascular diseases.
Subject: NLRP3 inflammasome activation
density lipoprotein
extracellular vesicle
high
low
oxidised lipoprotein
serum amyloid A
COMPLEX
high-density lipoprotein
RECEPTOR
ALPHA
AUTOPHAGY
MONOCYTIC CELLS
low-density lipoprotein
HIGH-DENSITY-LIPOPROTEIN
RESPONSES
PROTEIN-SAA
DEGRADATION
EXPRESSION
1182 Biochemistry, cell and molecular biology
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