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

Seunghwan Son, Inhwa Hwang, Seung Hyeokhan, Jeon Soo Shin, Ok Sarah Shin, Je Wook Yu

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 marrowderived 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.

Original languageEnglish
Pages (from-to)20437-20448
Number of pages12
JournalJournal of Biological Chemistry
Volume292
Issue number50
DOIs
Publication statusPublished - 2017 Dec 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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