|
KMID : 0359920140330010033
|
|
Korean Journal of Nephrology
2014 Volume.33 No. 1 p.33 ~ p.42
|
|
|
Effects of Toll-like receptor antagonist 4,5-dihydro-3-phenyl- 5-isoxasole acetic acid on the progression of kidney disease in mice on a high-fat diet
|
|
Min Hye-Sook
Kim Jung-Eun
Lee Mi-Hwa
Song Hye-Kyoung
Lee Mi-Jin
Lee Ji-Eun
Kim Hyun-Wook
Cha Jin-Joo
Hyun Young-Youl
Han Jee-Young
Cha Dae-Ryong
Kang Young-Sun
|
|
|
Abstract
|
|
|
Background: Obesity-related metabolic disorders are closely associated with in?ammation induced by innate immunity. Toll-like receptors (TLRs) play a pivotal role in the innate immune system by activating proin?ammatorysignaling pathways. GIT27 (4,5-dihydro-3-phenyl-5-isoxasole acetic acid) is an active immunomodulatory agent that primarily targets macrophages and inhibits secretion of tumor necrosis factor α [as well as interleukin (IL)-1β, IL-10, and interferon g]. However, the effect of TLR antagonist on kidney diseases has rarely been reported. We investigated whether the TLR antagonist GIT27 has bene?cial effects on the progression of kidney disease in obese mice on a high-fat diet (HFD).
Methods: Six-week-old male C57BL/6 mice were divided into three groups: mice fed with normal chow diet (N¼4); mice fed with a HFD (60% of total calories from fat, 5.5% from soybean oil, and 54.5% from lard, N¼4); and GIT27-treated mice fed with a HFD (N¼7).
Results: Glucose intolerance, oxidative stress, and lipid abnormalities in HFD mice were improved by GIT27 treatment. In addition, GIT27 treatment decreased the urinary excretion of albumin and protein in obesity-related kidney disease, urinary oxidative stress markers, and in?ammatory cytokine levels. This treatment inhibited the expression of proin?ammatory cytokines in the kidneys and adipose tissue, and improved extracellular matrix expansion and tubulointerstitial ?brosis in obesity- related kidney disease.
Conclusion: TLR inhibition by administering GIT27 improved metabolic parameters. GIT27 ameliorates abnormalities of lipid metabolism and may have renoprotective effects on obesity-related kidney disease through its anti-in?ammatory properties.
& 2014.The Korean Society of Nephrology.Published by Elsevier. All rights reserved.
|
|
|
KEYWORD
|
|
|
Kidney disease, Metabolic syndrome, Obesity, Toll-likereceptors
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|