Resistin increases the expression of NOD2 in mouse monocytes

Ren,Yi; Wan,Taomei; Zuo,Zhicai; Cui,Hengmin; Peng,Xi; Fang,Jing; Deng,Junliang; Hu,Yanchun; Yu,Shuming; Shen,Liuhong; Ma,Xiaoping; Wang,Ya; Ren,Zhihua

doi:10.3892/etm.2017.4288

Resistin increases the expression of NOD2 in mouse monocytes

Authors:
- Yi Ren
- Taomei Wan
- Zhicai Zuo
- Hengmin Cui
- Xi Peng
- Jing Fang
- Junliang Deng
- Yanchun Hu
- Shuming Yu
- Liuhong Shen
- Xiaoping Ma
- Ya Wang
- Zhihua Ren
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Affiliations: Sichuan Province Key Laboratory of Animal Disease and Human Health, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, P.R. China
Published online on: March 30, 2017 https://doi.org/10.3892/etm.2017.4288
Pages: 2523-2528

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Abstract

Previous studies have indicated that resistin, a type of adipokine, contributes to the development of insulin resistance and type 2 diabetes mellitus, and mediates inflammatory reactions. However, a specific receptor for resistin has not yet been identified. In this study, the relationship between resistin and nucleotide‑binding oligomerization domain‑like receptors, as well as resistin signal transduction, was examined through transfection, quantitative polymerase chain reaction, western blot analysis and ELISA. The mRNA expression of nucleotide‑binding oligomerization domain‑containing protein 2 (NOD2), a key immune receptor related to insulin resistance, was significantly increased by resistin treatment at concentrations of 100, 150 and 200 ng/ml (P<0.05, P<0.01 and P<0.01, respectively). The mRNA expression of downstream signaling molecules in the NOD2 signaling pathway, receptor‑interacting serine/threonine‑protein kinase 2 (RIP2; P<0.01 at 6, 12 and 24 h) and inhibitor of NF‑κB kinase subunit beta (P<0.01 at 3, 6, 12 and 24 h) were significantly increased by resistin treatment compared with the control. The mRNA expression of key proinflammatory cytokines, tumor necrosis factor α, IL (interleukin)‑6 and IL‑1β, were also significantly increased by resistin treatment compared with the control (P<0.01). NOD2 knockdown by small interfering RNA (siRNA) significantly decreased the expression of NOD2 and RIP2 (P<0.01), and there was no significant increase in the levels of cytokines, as compared with treatment with control siRNA. These findings indicate that the inflammatory reaction induced by resistin involves the NOD2‑nuclear factor (NF)‑κB signaling pathway. The inhibition of NF‑κB significantly decreased the secretion of key inflammatory cytokines (P<0.01), suggesting that NF‑κB signaling mechanisms are essential to the resistin‑induced inflammatory response.

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