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 organization: HUS Internal Medicine and Rehabilitation
TRIMM - Translational Immunology Research Program
Reumatologian yksikkö
Departments of Faculty of Veterinary Medicine
Medicum
Research Programs Unit
HUS Inflammation Center
Clinicum
Department of Medicine
HUS Musculoskeletal and Plastic Surgery
Molecular and Integrative Biosciences Research Programme
Biosciences
Date: 2021
Language: eng
Number of pages: 20
Belongs to series: Clinical Translational Immunology
ISSN: 2050-0068
DOI: https://doi.org/10.1002/cti2.1323
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
3121 General medicine, internal medicine and other clinical medicine
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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