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Advanced glycation end products impair NLRP3 inflammasome-mediated innate immune responses in macrophages

Authors
 Seunghwan Son  ;  Inhwa Hwang  ;  Seung Hyeok Han  ;  Jeon-Soo Shin  ;  Ok Sarah Shin  ;  Je-Wook Yu 
Citation
 Journal of Biological Chemistry, Vol.292(50) : 20437-20448, 2017 
Journal Title
 Journal of Biological Chemistry 
ISSN
 0021-9258 
Issue Date
2017
MeSH
Animals ; Biomarkers/metabolism ; Bone Marrow Cells/cytology ; Bone Marrow Cells/drug effects ; Bone Marrow Cells/immunology ; Bone Marrow Cells/metabolism ; Caspase 1/genetics ; Caspase 1/metabolism ; Cells, Cultured ; Down-Regulation*/drug effects ; Gene Expression Regulation/drug effects ; Genes, Reporter/drug effects ; Glycation End Products, Advanced/metabolism* ; Immunity, Innate*/drug effects ; Inflammasomes/drug effects ; Inflammasomes/immunology ; Inflammasomes/metabolism* ; Interleukin-1beta/genetics ; Interleukin-1beta/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Lipopolysaccharides/antagonists & inhibitors ; Lipopolysaccharides/toxicity ; Macrophage Activation*/drug effects ; Macrophages/cytology ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism* ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Specific Pathogen-Free Organisms
Keywords
NLRP3 ; glycation ; inflammasome ; innate immunity ; macrophage
Abstract
Advanced glycation end products (AGEs) are adducts formed on proteins by glycation with reducing sugars, such as glucose, and tend to form and accumulate under hyperglycemic conditions. AGE accumulation alters protein function and has been implicated in the pathogenesis of many degenerative diseases such as diabetic complications. AGEs have also been shown to promote the production of pro-inflammatory cytokines, but the roles of AGEs in inflammasome signaling have not been explored in detail. Here, we present evidence that AGEs attenuate activation of the NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) as determined by caspase-1 processing and interleukin-1β production. AGEs also dampened the assembly of the NLRP3 inflammasome, but did not affect the NLRC4 or AIM2 inflammasome activation. Moreover, our data indicated that AGE treatment inhibited Toll-like receptor (TLR)-dependent production of pro-inflammatory cytokines in BMDMs. This immunosuppressive effect of AGE was not associated with a receptor for AGEs (RAGE)-mediated signaling. Instead, AGE treatment markedly suppressed lipopolysaccharide-induced M1 polarization of macrophages. Furthermore, AGEs significantly dampened innate immune responses including NLRP3 inflammasome activation and type-I interferon production in macrophages upon influenza virus infection. These observations collectively suggest that AGEs could impair host NLRP3 inflammasome-mediated innate immune defenses against RNA virus infection leading to an increased susceptibility to infection.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/161507
DOI
10.1074/jbc.M117.806307
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
신전수(Shin, Jeon Soo) ; 유제욱(Yu, Je Wook) ; 한승혁(Han, Seung Hyeok) ; 황인화(Hwang, Inhwa)
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Full Text
http://www.jbc.org/content/292/50/20437.long
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