제1저자 손승환(미생물학교실, BK21)
교신저자 유제욱(미생물학교실, BK21)
J Biol Chem. 2017 Dec 15(50):20437-20448. doi: 10.1074/jbc.M117.806307. Epub 2017 Oct 19.
Advanced glycation end products impair NLRP3 inflammasome-mediated innate immune responses in macrophages.
Son S1, Hwang I1, Han SH2, Shin JS1, Shin OS3, Yu JW4.
From the Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science.
the Department of Internal Medicine, Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul 03722, Korea and.
the Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea.
From the Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, email@example.com.
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.