Natural killer T cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein E-deficient mice

Andoh, Yasuhiro; Ogura, Hisako; Satoh, Masashi; Shimano, Kentaro; Okuno, Hironori; Fujii, Satoshi; Ishimori, Naoki; Eshima, Koji; Tamauchi, Hidekazu; Otani, T.; Nakai, Yukihito; Kaer, Luc Van; Tsutsui, Hiroyuki; Onoé, Kazunori; Iwabuchi, Kazuya

doi:10.1016/j.imbio.2012.07.022

Cited by 21 publications

(11 citation statements)

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“…It must be pointed out that LPS injection is known to aggravate atherosclerosis. However, in in vivo studies, the route of LPS injection is limited to intravenous or intraperitoneal, and the doses of LPS usually range between 0.5 mg/kg and 2.5 mg/kg BW, which is sufficient to cause atherosclerosis in apoE-deficient mice [ 49 – 51 ]. On the other hand, oral administration of LPSp at a high dose (300 mg/kg BW, 4 weeks) caused no significant hepatotoxicity or nephrotoxicity in rat [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents development of atherosclerosis in high-fat diet-fed apoE-deficient mice via ameliorating hyperlipidemia, pro-inflammatory mediators and oxidative responses

et al. 2018

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Pantoea agglomerans (P. agglomerans) is a Gram-negative bacterium that grows symbiotically with various edible plants, and the oral or sublingual administration of lipopolysaccharide derived from P. agglomerans (LPSp) have been suggested to contribute to prevention of immune-related diseases. Our previous study indicated that orally administered LPSp was shown to exhibit an LDL-lowering effect in hyperlipidemic volunteers; however, a preventive effect of LPSp on atherosclerosis is unclear. The present study attempted to evaluate the anti-atherosclerotic effect by LPSp in a mouse model of high-fat diet (HFD)-induced atherosclerosis. For 16 weeks, apoE-deficient mice were fed an HFD and received drinking water containing LPSp (0.3 or 1 mg/kg body weight/day). The results showed that the orally administered LPSp decreased body weight. A significant reduction in atherosclerotic plaque deposition was observed even with the lower dose of LPSp. The biochemical analyses showed that LPSp markedly improved glucose tolerance and reduced plasma LDL and oxidized LDL levels. In addition, LPSp significantly reduced the production of pro-inflammatory mediators including MCP-1 (in the plasma), TNF-α and IL-6 (in the colon), and decreased the oxidative burst activities in the peripheral blood sample. Taken together, these results suggest the possibility that oral administration of LPSp can effectively ameliorate HFD-induced hyperlipidemia and inflammatory/oxidative responses to prevent atherosclerosis and related metabolic disorders.

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Section: Discussionmentioning

confidence: 99%

Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents development of atherosclerosis in high-fat diet-fed apoE-deficient mice via ameliorating hyperlipidemia, pro-inflammatory mediators and oxidative responses

et al. 2018

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“…During normal homeostasis there are a high number of iNKT cells in the adipose tissue, while in the obesity their proportion is disturbed and these cells possess increased capacity of production of the proinflammatory cytokines [28]. NKT cells and especially iNKT cells were also shown to contribute to the pathophysiology of atherosclerosis, a well-known complication of OSAS [29, 30]. Unfortunately, we investigated NKT cells without precise discrimination to iNKT which needs further investigation in OSAS.…”

Section: Discussionmentioning

confidence: 99%

T, B, and NKT Cells in Systemic Inflammation in Obstructive Sleep Apnoea

Domagała‐Kulawik

Osińska

Piechuta

et al. 2015

Mediators of Inflammation

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Background. Obstructive sleep apnoea syndrome (OSAS) brings risk of serious complications. The study objective was to assess elements of the cellular immune response in the course of OSAS. Methods. Peripheral blood (PB) lymphocytes: T, B, NK, NKT-like, Th, Tc, and HLA DR+ T cells were evaluated by flow cytometry of 48 OSA patients; the concentration of adiponectin, interleukin 1β, and TNFα was measured by ELISA method. The OSA complication score was developed and used for statistical analysis. Results. The proportion of B cells and Th/Tc ratio were significantly lower in the BP of OSA patients when compared with control subjects (median 7.9 versus 10.9%, 0.9 versus 1.5, p < 0.05). The proportion of Tc, NK, NKT-like, and HLADR positive T cells were elevated in OSA patients when compared with healthy subjects (36.4 versus 26.8, 15.5 versus 8.5, 5.7 versus 3.0, and 8.4 versus 4.5%, p < 0.05, resp.) and were more pronounced in patients with metabolic syndrome. The grade of OSA complication score correlated with systemic inflammation markers and the proportion of B cells. The value of adiponectin/BMI ratio correlated significantly with SpO2 (r = 0.31, p < 0.05), CRP (r = −0.35, p < 0.05), TNFα concentration (r = −0.36, p < 0.05), and proportion of B cells (r = 0.32, p < 0.05). Conclusion. Lymphocytes B, Tc, NK, NKT-like, and adiponectin are involved in systemic immune response in OSA patients possibly predisposing them to cardiovascular and metabolic complications.

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“…It has been shown consistently that administration of low dose LPS (10–50 μg/mouse) in atherosclerosis-prone mice induces atherosclerosis 6–11 . Our laboratory has demonstrated that antagonizing Toll-like receptor (TLR)4, the receptor for LPS, reduces atherosclerosis 12, 13 .…”

Section: Introductionmentioning

confidence: 99%

Cooperative stimulation of atherogenesis by lipopolysaccharide and palmitic acid-rich high fat diet in low-density lipoprotein receptor-deficient mice

Brinson

et al. 2017

Atherosclerosis

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Background and aims Either lipopolysaccharide (LPS) or high-fat diet (HFD) enriched with saturated fatty acid (SFA) promotes atherosclerosis. In this study, we investigated the effect of LPS in combination with SFA-rich HFD on atherosclerosis and how LPS and SFA interact to stimulate inflammatory response in vascular endothelial cells. Methods Low-density lipoprotein receptor-deficient (LDLR−/−) mice were fed low-fat diet (LFD), HFD with low palmitic acid (PA) (LP-HFD), or HFD with high PA (HP-HFD) for 20 weeks. During the last 12 weeks, half mice received LPS and half received PBS. After treatment, metabolic parameters and aortic atherosclerosis were analyzed. To understand the underlying mechanisms, human aortic endothelial cells (HAECs) were treated with LPS and/or PA and proinflammatory molecule expression was quantified. Results Metabolic study showed that LPS had no significant effect on cholesterol, triglycerides, free fatty acids, but increased insulin and insulin resistance. Both LP-HFD and HP-HFD increased body weight and cholesterol while LP-HFD increased glucose and HP-HFD increased triglycerides, insulin, and insulin resistance. Analysis of aortic atherosclerosis showed that HP-HFD was more effective than LP-HFD in inducing atherosclerosis and LPS in combination with HP-HFD increased atherosclerosis in the thoracic aorta, a less common site for atherosclerosis, as compared with LPS or HP-HFD. To understand the mechanisms, results showed that LPS and PA synergistically upregulated adhesion molecules and proinflammatory cytokines in HAECs. Conclusions LPS and PA-rich HFD cooperatively increased atherogenesis in the thoracic aorta. The synergy between LPS and PA on proinflammatory molecules in HAECs may play an important role in atherogenesis.

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Natural killer T cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein E-deficient mice

Cited by 21 publications

References 50 publications

Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents development of atherosclerosis in high-fat diet-fed apoE-deficient mice via ameliorating hyperlipidemia, pro-inflammatory mediators and oxidative responses

Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents development of atherosclerosis in high-fat diet-fed apoE-deficient mice via ameliorating hyperlipidemia, pro-inflammatory mediators and oxidative responses

T, B, and NKT Cells in Systemic Inflammation in Obstructive Sleep Apnoea

Cooperative stimulation of atherogenesis by lipopolysaccharide and palmitic acid-rich high fat diet in low-density lipoprotein receptor-deficient mice

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