ABSTRACT
BACKGROUND: Obesity-related metabolic disorders are closely associated with inflammation induced by innate immunity. Toll-like receptors (TLRs) play a pivotal role in the innate immune system by activating proinflammatory signaling 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 alpha [as well as interleukin (IL)-1beta, IL-10, and interferon gamma]. However, the effect of TLR antagonist on kidney diseases has rarely been reported. We investigated whether the TLR antagonist GIT27 has beneficial 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 (N=4); mice fed with a HFD (60% of total calories from fat, 5.5% from soybean oil, and 54.5% from lard, N=4); and GIT27-treated mice fed with a HFD (N=7). 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 inflammatory cytokine levels. This treatment inhibited the expression of proinflammatory cytokines in the kidneys and adipose tissue, and improved extracellular matrix expansion and tubulointerstitial fibrosis 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-inflammatory properties.
Subject(s)
Animals , Humans , Male , Mice , Acetic Acid , Adipose Tissue , Cytokines , Diet , Diet, High-Fat , Extracellular Matrix , Fibrosis , Glucose Intolerance , Immune System , Immunity, Innate , Inflammation , Interferons , Interleukin-10 , Interleukins , Kidney , Kidney Diseases , Lipid Metabolism , Macrophages , Mice, Obese , Obesity , Oxidative Stress , Soybean Oil , Toll-Like Receptors , Tumor Necrosis Factor-alphaABSTRACT
Objective To study the level of the Toll like-receptor mRNA expression on PBMCs from patients with the idiopathic thrombocytopenic purpura.Methods We performed quantitative real-time reverse transcription-polymerase chain reaction(SYBR Green Ⅰ fluorescent dye combination technique)analyses of PBMCs from 30 idiopathic thrombocytopenic purpura(ITP) patients and 30 healthy subjects,to estimate the relative levels of TLR2,TLR4,TLR6,TLR7 and TLR9 mRNA expression.Results Relative expression levels of TLR2 and TLR7 mRNAs in ITP group(n=30)were significantly higher than those in health control group(n=30)(P0.05).Conclusion Expressions of TLR2 and TLR7 mRNA are up-regulated in patients with ITP,which may play an important role in the pathogenesis of ITP.