LPS-stimulated Macrophage Activation Affects Endothelial Dysfunction

Abstract

Intestinal microbiota is involved in the atherosclerotic process by development of an atheromatous core with foam cells in carotid arteries. It has reported that lipopolysaccharide (LPS) from Escherichia coli localizes in human atherosclerotic plaque and causes inflammation via interaction with toll like receptor 4. However, there is no evidence that whether LPS-activated macrophages regulate endothelial cell (EC) function. We evaluated whether LPS-activated macrophage acts as one of the stimulants activating EC and its underlying signaling pathways. Using Western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we confirmed that intraperitoneal injection with LPS increases iNOS protein and inflammatory cytokine, TNF-α and IL-6 mRNA expressions. To determine whether LPS-mediated macrophage inflammatory condition affects EC activation and inflammation, human umbilical vein endothelial cells (HUVECs) were incubated with isolated peritoneal macrophages from LPS-injected mice. Interestingly, p90RSK Serine 380 phosphorylation and protein expression were significantly increased by macrophage treatment in EC. Messenger RNA levels of vascular cell adhesion molecule 1 and p90RSK was increased, but endothelial nitric oxide synthase was decreased. In addition, NF-κB promoter activity, which plays an important role in the pathogenesis of inflammation, was strongly enhanced by the macrophage treatment in EC. We further evaluated the effects of LPS on EC function in the mouse aorta using en face staining. In agreement with in vitro result, p90RSK expression was strongly increased in the steady laminar flow region of the mouse aorta in mice injected with LPS. Together, our study demonstrates that p90RSK might be a one of the major therapeutic candidates for the prevention of vascular diseases mediated by LPS.

Preventive Effects of Alpha-Lipoic Acid on Lipopolysaccharide-Induced Endothelial Dysfunction in Rats

“…In vivo, LPS E. coli (0.05 mg.mL -1 LPS in PBS or 0.5 mg.kg -1 BW i.p) could induce endothelial dysfunction in 24 hours through increasing protein expression in endothelial cells, such as LOX-1, NFκB, and p38-mitogen-activated protein kinase (MAPK) (Zhao et al, 2014). The LPS-mediated inflammatory environment also affects iNOS, TNFα and IL-6 mRNA levels in a concentration-dependent manner (Baek et al, 2018). Since it was known that LD50 of E. coli LPS i.p in the rat is 5 mg.kg -1 BW, and minimum dose 1 mg.kg -1 BW still caused some deaths in 24 hours (Ashour et al, 2011), thus in this present study LPS dose 0.5 mg.kg -1 BW was used.…”

“…Lipopolysaccharideinduced VCAM-1 expression (Jiang et al, 2013) and leukocyte adhesion in lung tissue (Wu et al, 2012). In vitro, LPS also promoted VCAM-1 expression and other adhesion molecules in human umbilical cord vein cell (HUVEC) (Liu et al, 2012;Wu et al, 2012, Baek et al, 2018, mesangial cell (Lee et al, 2012); vascular smooth muscle cell (Meng et al, 2013); mouse glial and neuronal cultures (Leow-Dyke et al, 2012). The mechanism involves TLR-4 stimulation, then trigger LPS 0.5mg.kg-1 BW i.p.…”

Effect of Laparatomy and Lipopolysaccharide-Induced Systemic Inflammatory Response on Metabolic Disorders in Rats

“…Введення ЛПС S. typhi «хибнооперова- Якщо зростання активності iNOS у сироватці крові, вочевидь, супроводжує процес диференціювання моноцитів у макрофаги М1 у відповідь на дію ЛПС та прозапальних цитокінів [23], то активність cNOS імовірно зменшується внаслідок ендотеліальної дисфункції, що може викликатися цими самими чинниками [24]. Ураження ендотелію за умов хірургічної травми сприяє як механічне ушкодження тканин, так і гіпоперфузія, ішемія/реперфузія, підвищення напруження зсуву, гіповолемія, гіперглікемія, оксидативний стрес, СЗВ та коагулопатія [1].…”