Irisin Alleviates Advanced Glycation End Products-Induced Inflammation and Endothelial Dysfunction via Inhibiting ROS-NLRP3 Inflammasome Signaling.

Abstract

The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome have been implicated in the initiation or progression of atherosclerosis. Recent research showed that irisin, a newly discovered adipomiokine, alleviates endothelial dysfunction in type 2 diabetes partially via reducing oxidative/nitrative stresses, suggesting that irisin may be a promising candidate for the treatment of vascular complications of diabetes. However, the association between irisin and NLRP3 inflammasome in the pathogenesis of atherosclerosis remains unclear. In the present study, we cultured human umbilical vein endothelial cells (HUVECs) in advanced glycation end products (AGEs) medium; exogenous irisin (0.01, 0.1, 1 μg/ml) were used as an intervention reagent. siRNA and adenoviral vector were constructed to realize silencing and over-expression of NLRP3 gene. Our data showed that irisin significantly reversed AGEs-induced oxidative stress and NLRP3 inflammasome signaling activation (p < 0.05), and increased the endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production in a dose-dependent manner (p < 0.05). siRNA-mediated knockdown NLRP3 facilitated the irisin-mediated anti-inflammatory and antiatherogenic effects (p < 0.05). However, these irisin-mediated effects were reversed by over-expression NLRP3 (p < 0.05). Taken together, our results reveal that irisin alleviates AGEs-induced inflammation and endothelial dysfunction via inhibiting ROS-NLRP3 inflammasome signaling, suggest a likely mechanism for irisin-induced therapeutic effect in vascular complications of diabetes.

• Authors: Xian Deng, Wei Huang, Juan Peng, Ting-Ting Zhu, Xiao-Lei Sun, Xiang-Yu Zhou, Hui Yang, Jian-Feng Xiong, Hu-Qiang He, You-Hua Xu, Yan-Zheng He
• Journal: Inflammation (Inflammation) Vol. 41 Issue 1 Pg. 260-275 (Feb 2018) ISSN: 1573-2576 [Electronic] United States
• PMID: 29098483 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• FNDC5 protein, human
• Fibronectins
• Glycation End Products, Advanced
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Reactive Oxygen Species
• Nitric Oxide
• NOS3 protein, human
• Nitric Oxide Synthase Type III

Topics

• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects, metabolism)
• Fibronectins (pharmacology)
• Glycation End Products, Advanced (toxicity)
• Humans
• Inflammation (chemically induced, genetics, metabolism, prevention & control)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Oxidative Stress (drug effects)
• RNA Interference
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Time Factors
• Transfection