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.
|Number of pages||12|
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 2017 Dec 15|
Bibliographical noteFunding Information:
This work was supported by National Research Foundation of Korea Grants 2014R1A4A1008625, 2015M3A9B6073856, and 2017R1A2B2007467 from the Korean Government and Yonsei University College of Medicine Faculty Research Grant 6-2016-0090. The authors declare that they have no con-flicts of interest with the contents of this article.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology