KMID : 0578320180410080762
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Molecules and Cells 2018 Volume.41 No. 8 p.762 ~ p.770
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Globular Adiponectin Exerts a Pro-Inflammatory Effect via I¥êB/NF-¥êB Pathway Activation and Anti-Inflammatory Effect by IRAK-1 Downregulation
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Lee Kyoung-Hee
Jeong Ji-Yeong Woo Ji-Su Lee Chang-Hoon Yoo Chul-Gyu
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Abstract
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Adiponectin, a hormone produced by adipose tissue, is very abundant in plasma, and its anti- and pro-inflammatory effects are reported. However, the mechanisms of these pro- and anti-inflammatory effects are not fully defined. Herein, we evaluated the dual inflammatory response mechanism of adiponectin in macrophages. Short-term globular adiponectin (gAd) treatment induced I¥êB¥á degradation, NF-¥êB nuclear translocation, and TNF-¥á production in RAW 264.7 cells. Polymyxin B pretreatment did not block gAd-induced I¥êB¥á degradation, and heated gAd was unable to degrade I¥êB¥á, suggesting that the effects of gAd were not due to endotoxin contamination. gAd activated IKK and Akt, and inhibition of either IKK or Akt by dominant-negative IKK¥â (DN-IKK¥â) or DN-Akt overexpression blocked gAd-induced I¥êB¥á degradation, suggesting that short-term incubation with gAd mediates inflammatory responses by activating the I¥êB/NF-¥êB and PI3K/Akt pathways. Contrastingly, long-term stimulation with gAd induced, upon subsequent stimulation, tolerance to gAd, lipopolysaccharide, and CpG-oligodeoxynucleotide, which is associated with gAd-induced downregulation of IL-receptor-associated kinase-1 (IRAK-1) due to IRAK-1 transcriptional repression. Conclusively, our findings demonstrate that the pro- and anti-inflammatory responses to gAd in innate immune cells are time-dependent, and mediated by the activation of the I¥êB/NF-¥êB pathway, and IRAK-1 downregulation, respectively.
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KEYWORD
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globular adiponection, NF-¥êB, IRAK-1
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