Chylomicron remnants upregulate CD40 expression via the ERK pathway and a redox-sensitive mechanism in THP-1 cells

J. Clin. Biochem. Nutr.

Katagiri

et al. 2011

Self Cite

In inflammatory bowel diseases, interleukin-1β production is accelerated. Butyrate, a short chain fatty acid, plays an important role in inflammatory bowel diseases. We investigated the effect of butyrate on interleukin-1β production in macrophage and elucidated its underlying mechanism. We stimulated THP-1 cells, a human premonocytic cell line, by lipopolysaccharide alone and by butyrate with lipopolysaccharide. Butyrate with lipopolysaccharide increased interleukin-1β production more than lipopolysaccharide alone. Butyrate with lipopolysaccharide increased caspase-1 activity more than lipopolysaccharide alone. As for the phosphorylation pathway, PD98059 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor) decreased caspase-1 activity and interleukin-1β production to approximately 50% of the controls. Pertussis toxin (G protein-coupled signal transduction pathway inhibitor) also reduced interleukin-1β production to approximately 50%. Butyrate with lipopolysaccharide increased reactive oxygen species levels more than lipopolysaccharide alone. The addition of N-acetyl L-cysteine reduced reactive oxygen species levels to a level similar to that of lipopolysaccharide alone. Butyrate with lipopolysaccharide increased nitric oxide production more than lipopolysaccharide alone, and the addition of N-acetyl L-cysteine reduced the elevated amount of nitric oxide. In conclusions, butyrate enhances interleukin-1β production by activating caspase-1, via reactive oxygen species, the phosphorylation of MAPK, and G protein mediated pathways in lipopolysaccharide stimulated THP-1 cells.

Section: Methodsmentioning

confidence: 99%

“…(8,9) The positive control cells were treated with 0.1 µg/ml LPS alone for 6 h (caspase-1 assay) or 24 h (IL-1β assay).…”

Section: Methodsmentioning

confidence: 99%

Butyrate enhancement of inteleukin-1β production via activation of oxidative stress pathways in lipopolysaccharide-stimulated THP-1 cells

Ohira

J. Clin. Biochem. Nutr.

Katagiri

et al. 2011

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“…CD40, a cell membranespanning protein that belongs to the family of tumor necrosis factor receptors and mediates the activation and differentiation of B-lymphocytes, is expressed in cells found in atherosclerotic lesions and is associated with the expression of matrix metalloproteinases, procoagulant tissue factors, chemokines, cytokines, and adhesion molecules in vascular cells 70) . We reported that physiological concentrations of chylomicron remnants upregulated the expression of CD40 without affecting the viability of THP-1 cells and peripheral blood mononuclear cells by the extracellular signalregulated kinase 1/2 mediated pathway, which was followed by the redox-sensitive mechanism-dependent and -independent pathway 71) . Thus, chylomicron remnants may contribute to lesion formation not only by lipid supplementation but also by activation of inflammation.…”

Section: Macrophagesmentioning

confidence: 97%

Remnant Lipoproteins As Strong Key Particles to Atherogenesis

Ishikawa

2009

J Atheroscler Thromb

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121

115

Recent epidemiologic studies have revealed that hypertriglyceridemia is associated with atherosclerosis independent of other coronary risk factors. However, it is difficult to select patients at high risk for coronary artery disease using only serum triglyceride levels compared with low-density lipoprotein cholesterol levels since multiple factors are associated with elevating triglycerides. Atherosclerotic diseases with high triglyceride levels can be found in patients with familial combined hyperlipidemia, diabetes mellitus, and metabolic syndrome, in which remnant lipoproteins accumulate in the circulating blood. Recent researches have paid attention to remnant lipoproteins as atherogenic particles with the development of methods for measuring remnant cholesterol levels and apolipoprotein B-48 levels directly from human serum. Measurement of these parameters in addition to serum triglycerides may help to distinguish high-risk patients and enable us to prevent or suppress the progression of atherosclerotic diseases in those patients. However, questions remain to be answerd to evaluate the significance of remnant lipoproteins. Here, we focus on three issues: the underlying problems in measuring remnant lipoprotein cholesterol, the assessment of postprandial hyperlipidemia as an atherogenic condition, and finally a review of our experimental and clinical findings about the mechanisms by which remnant lipoproteins induce atherosclerosis.

“…Their age was 62. 6 1.4 years old (mean SEM), and their body mass indices (BMI) were 24.7 0.5 (mean SEM). Because this study included 47 patients with diabetes mellitus, HbA1c and FPG levels were elevated compared to the normal standard range.…”

Section: Resultsmentioning

confidence: 99%

“…Besides hs-CRP, several inflammatory biomarkers are associated with atherosclerosis, including soluble endothelial-leukocyte adhesion molecules, soluble CD40 ligand, tumor necrosis factor (TNF)-interleukin (IL)-1 , IL-6, and IL-18 2,5,6) . IL-18 is known to exist in the atherosclerotic plaque and plays an important role in the rupture of unstable plaque [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Pitavastatin Reduces Elevated IL-18 Levels in Japanese Subjects with Hypercholesterolemia: Sub-analysis of Kansai Investigation of Statin for Hyperlipidemic Intervention in Metabolism and Endocrinology (KISHIMEN)

Fukuda

Ishida

et al. 2011

JAT

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Aim: Pitavastatin significantly improved lipid profiles and reduced serum high-sensitivity C-reactive protein (hs-CRP) levels in a multi-center and prospective study. The aim of this study was to explore the effect of pitavastatin on serum levels of another inflammatory biomarker, interleukin-18 (IL-18), in a sub-analysis of the previous multi-center prospective study. Methods: The subjects were 83 patients derived from the KISHIMEN study. Pitavastatin (1-2 mg/ day) was administered for 12 months. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG), IL-18, and high sensitivity C-reactive protein (hs-CRP) levels were measured. Results: TC, LDL-C, and RLP-C levels were significantly reduced by 18.3%, 30.1%, and 21.0% (mean values) at 12 months after pitavastatin administration. TG levels were decreased by 9.8% in subjects whose basal TG levels were above 150 mg/dL. HDL-C levels were significantly increased at 6 months (11.9%). Pitavastatin did not significantly alter IL-18 levels in overall subjects, but reduced IL-18 levels in the highest quartile by 24.5% (median value) at 12 months. Pitavastatin significantly reduced hs-CRP levels by 28.6% in overall subjects and by 62.4% in the highest quartile at 12 months. There was a significant correlation between IL-18 and hs-CRP at baseline after both values were transformed into logarithms (Pearson's correlation coefficient, r 0.259, p 0.0181); however, percent changes in these levels were not significantly correlated. Conclusion: Pitavastatin significantly improves lipid profiles, and reduces enhanced inflammation monitored by IL-18, as well as by hs-CRP, in hypercholesterolemic subjects. J Atheroscler Thromb, 2011; 18:8-15.