Lipopolysaccharide (LPS) Stimulates the Production of Tumor Necrosis Factor (TNF)-α and Expression of Inducible Nitric Oxide Synthase (iNOS) by Osteoclasts (OCL) in Murine Bone Marrow Cell Culture

ABSTRACT The role of dendritic cells (DC) in urinary tract infections (UTI) is unknown. These cells contribute directly to the innate defense against various viral and bacterial infections. Here, we studied their role in UTI using an experimental model induced by transurethral instillation of the uropathogenic Escherichia coli (UPEC) strain 536 into C57BL/6 mice. While few DC were found in the uninfected bladder, many had been recruited after 24 h, mostly to the submucosa and uroepithelium. They expressed markers of activation and maturation and exhibited the CD11b+ F4/80+ CD8− Gr-1− myeloid subtype. Also, tumor necrosis factor alpha (TNF-α)- and inducible nitric oxide synthase (iNOS)-producing CD11bINT DC (Tip-DC) were detected, which recently were proposed to be critical in the defense against bacterial infections. However, Tip-DC-deficient CCR2−/− mice did not show reduced clearance of UPEC from the infected bladder. Moreover, clearance was also unimpaired in CD11c-DTR mice depleted of all DC by injection of diphtheria toxin. This may be explained by the abundance of granulocytes and of iNOS- and TNF-α-producing non-DC that were able to replace Tip-DC functionality. These findings demonstrate that some of the abundant DC recruited in UTI contributed innate immune effector functions, which were, however, dispensable in the microenvironment of the bladder.

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Metformin inhibits expression of the proinflammatory biomarker inducible nitric oxide synthase in hepatocytes

Functional Foods in Health and Disease ◽

10.31989/ffhd.v8i3.423 ◽

2018 ◽

Vol 8 (3) ◽

pp. 175 ◽

Cited By ~ 2

Author(s):

Richi Nakatake ◽

Hiroya Iida ◽

Morihiko Ishizaki ◽

Kosuke Matsui ◽

Yusuke Nakamura ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Tumor Necrosis ◽

Type I ◽

Tnf Α ◽

Oxide Synthase ◽

Necrosis Factor ◽

Inducible Nitric Oxide ◽

Inos Induction

Background: Metformin is used to treat patients with type II diabetes. However, there are few scientific reports on its anti-inflammatory effects. In the inflamed liver, proinflammatory cytokines stimulate liver cells, followed by inducible nitric oxide synthase (iNOS) expression. Excessive NO levels produced by iNOS have been implicated as a factor in liver injury. As a result, it is essential to inhibit iNOS induction to prevent liver injury.Objective: This study aimed to investigate liver protective effects of metformin by examining interleukin (IL)-1β-stimulated hepatocytes. Methods: Primary cultured rat hepatocytes were treated with interleukin (IL)-1β in the presence or absence of metformin. iNOS induction and its signaling pathway were analyzed.Results: Metformin decreased iNOS protein and mRNA expression, resulting in the inhibition of hepatic NO production. Metformin also reduced tumor necrosis factor (TNF)-α and IL-6 mRNA expression. Metformin inhibited an essential signaling pathway for iNOS induction, type I IL-1 receptor upregulation. Transfection experiments revealed that metformin reduced iNOS mRNA levels through both promoter transactivation and mRNA stabilization. Delayed metformin administration after IL-1β addition also inhibited iNOS induction. Conclusions: Metformin affects the induction of inflammatory mediators including iNOS and TNF-α, demonstrating its therapeutic potential for organ injuries, including the liver.Keywords: metformin, inducible nitric oxide synthase, liver injury, primary cultured hepatocytes, type I interleukin-1 receptor, tumor necrosis factor-α

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Inducible Nitric Oxide Synthase and Tumor Necrosis Factor-Alpha in Myocardium in Human Dilated Cardiomyopathy

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(96)00567-0 ◽

1997 ◽

Vol 29 (4) ◽

pp. 716-724 ◽

Cited By ~ 97

Author(s):

Mamoru Satoh ◽

Motoyuki Nakamura ◽

Gen Tamura ◽

Shinji Makita ◽

Ikuo Segawa ◽

...

Keyword(s):

Nitric Oxide ◽

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Inducible Nitric Oxide Synthase ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Oxide Synthase ◽

Necrosis Factor ◽

Inducible Nitric Oxide

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Alimentary induced fatty liver and adjuvant therapy with effective natural bioactive molecules

Orvosi Hetilap ◽

10.1556/oh.2011.29151 ◽

2011 ◽

Vol 152 (26) ◽

pp. 1035-1042 ◽

Cited By ~ 1

Author(s):

Viktor Hegedüs ◽

Domokos Gerő ◽

Zoltán Mihály ◽

Attila Szijártó ◽

Tivadar Zelles ◽

...

Keyword(s):

Nitric Oxide ◽

Fatty Liver ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Redox Homeostasis ◽

Mrna Levels ◽

Factor Α ◽

Oxide Synthase ◽

Necrosis Factor ◽

Inducible Nitric Oxide

Changes of redox-homeostasis generate cytokines, and free radicals influence many intracellular signaling pathways in different liver diseases. Liophylised table beet and carrot powder (GPS Powder Kft. 1361/004/2003BFÁÉÉÁ) containing bioactive components such as betaine, betanins, betaxanthins, flavonoids, polyphenols, glutamine, beta carotene, vitamins and folic acid may produce changes various cellular pathways. Aim: The aim of this study was to determine the protecting effects of bioactive agents of the liophylised table beet and carrot powder on fatty liver in a “short term” experiment. Method: Male Wistar rats were fed with chow with or without high fat (2% cholesterol, 0.5% cholic acid, 20% sunflower oil) and treated with 0.1 or 1 g/bwkg/day natural product for ten days parallel with the feedings. Cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels were determined using molecular biologic methods. Free radicals, H-donating activity, reducing power and free SH-group concentrations were determined by luminometry and spectrophotometry. Mobilized methyl groups were assayed by over pressure liquid chromatography method in liver homogenates. Results: It was found that the higher dose of the natural product better decreased the induced free radical reactions, cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α mRNA-levels both in normal and fatty liver tissues. Although treatments failed to exert significant changes in all global antioxidant parameters, mobilized methyl group concentrations were higher after treatments in fatty liver. Favorable tendencies were also noted in the redox-homeostasis of the fatty liver after treatment. Conclusions: As expected, lyophylised table beet and carrot proved to be a “functional food” in rats with alimentary fat induced fatty liver. It cannot be ruled out that this beneficial effect may have clinical relevance. Orv. Hetil., 2011, 152, 1035–1042.

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