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Modulation of Inflammasome Signaling by Advanced Glycation End Products (AGEs)
Author(s) -
Son SeungHwan,
Hwang Inhwa,
Yu JeWook
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb194
Subject(s) - inflammasome , aim2 , nlrc4 , inflammation , rage (emotion) , immune system , glycation , immunology , innate immune system , secretion , receptor , microbiology and biotechnology , medicine , chemistry , biology , caspase 1 , endocrinology , neuroscience
Deregulated immune response in obese condition leads to not only chronic inflammation but impaired protection against microbial infection such as influenza virus. The underlying mechanism by which obesity is related to the impaired host immune defense against pathogen invasion is poorly described. Here, we found that advanced glycation end products (AGEs), which are elevated in obese condition, specifically inhibit the activation of NLRP3 inflammasome in bone marrow‐derived macrophages (BMDMs). Pretreatment of AGEs attenuated diverse NLRP3 stimuli‐triggered caspase‐1 activation and interleukin‐1 beta (IL‐1β) secretion, but failed to affect AIM2‐ and NLRC4‐mediated inflammasome activation. AGEs also decreased ASC oligomerization and mitochondrial reactive oxygen species (ROS) production in response to NLRP3 inflammasome stimulator. However, treatment of receptor for AGEs (RAGE) antagonist FPS‐ZM1, did not alter the NLRP3 inflammasome‐suppressing effect of AGEs. Furthermore, AGEs abolished inflammasome activation triggered by poly I:C transfection or influenza virus infection. Taken together, our results suggest that AGEs potentially contributes to impaired innate immune response in obese condition by suppressing NLRP3 inflammasome signaling. Support or Funding Information This work was supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean Government (2015M3A9B6073856)