Altered functions of natural killer cells in response to L-Arginine availability

Lamas, Bruno; Vergnaud-Gauduchon, Juliette; Goncalves-Mendès, Nicolas; Perche, Olivier; Rossary, Adrien; Vasson, Marie‐Paule; Farges, Marie‐Chantal

doi:10.1016/j.cellimm.2012.11.018

Cited by 75 publications

(55 citation statements)

References 45 publications

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“…Basal expression of ROS-producing enzymes and basal ROS production. ROS-producing enzymes of mammary epithelial cells were characterized in our culture cell conditions without leptin by q-PCR using previously-described primers (Table I) (42,43). Of the different ROS-producing systems studied, i.e.…”

Section: Resultsmentioning

confidence: 99%

Leptin induces ROS via NOX5 in healthy and neoplastic mammary epithelial cells

et al. 2017

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NADPH oxidase (NOX) complexes (a family of seven isoforms) drive cellular ROS production in patho-logical processes such as cancer. NOX-driven ROS production is involved in cell mechanisms from signalling to oxidative stress. Leptin, an adipokine overexpressed in obese patients, has been investigated in studies on breast carcinogenesis, but its effects on oxidative stress remain largely unexplored, especially in breast cancer. The study used three human mammary epithelial cell models presenting different neoplastic status (healthy primary HMECs, neoplastic MCF-7 cells and neoplastic MDA-MB-231 cells) to determine the effects of leptin on short-term ROS production and to characterize the enzymes involved. All three cell models significantly expressed NADPH oxidase isoform 5 (NOX5) in our culture conditions. All models showed induced ROS production regardless of leptin concentration (10 ng/ml mimicking good health, 100 ng/ml mimicking obesity). Cell treatment with either siRNA against NOX5, NOX inhibitor DPI or a calcium channel blocker (verapamil) confirmed the putative involvement of the NOX5 isoenzyme in ROS production. Moreover, cell treatments suppressed ROS production under leptin at both concentrations. Neoplastic cells appeared unable to downregulate NOX5 mRNA expression under leptin. Leptin emerged as a potential activator of ROS production in human epithelial mammary cells, where the ROS production was apparently linked to NOX5 activation. This novel finding could shed light on the potential role of obesity-associated hyperleptinemia in mammary cells via the activation of NOX enzymes.

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Section: Resultsmentioning

confidence: 99%

Leptin induces ROS via NOX5 in healthy and neoplastic mammary epithelial cells

et al. 2017

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“…As L-arginine can directly regulate NK cell phenotype and function, the acute loss of L-arginine can profoundly affect NK cell responses (50). The effect on NK cell responses likely corresponds to the number of MDSCs and hence arginase-1 in the system (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus–Induced Myeloid-Derived Suppressor Cells Suppress NK Cell IFN-γ Production by Altering Cellular Metabolism via Arginase-1

Yergin

Roggerson

Lee

et al. 2016

The Journal of Immunology

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The hepatitis C virus (HCV) infects ~200 million people worldwide. The majority of infected individuals develop persistent infection, resulting in chronic inflammation and liver disease, including cirrhosis and hepatocellular carcinoma. HCV’s ability to establish persistent infection is partly due to its ability to evade the immune response through multiple mechanisms, including suppression of natural killer (NK) cells. NK cells control HCV replication during the early phase of infection and regulate the progression to chronic disease. In particular, IFN-γ produced by NK cells limits viral replication in hepatocytes and is important for the initiation of adaptive immune responses. However, NK cell function is significantly impaired in chronic HCV patients. The cellular and molecular mechanisms responsible for impaired NK cell function in HCV infection are not well defined. Here, we analyzed the interaction of human NK cells with CD33+ PBMCs that were exposed to HCV. We found that NK cells co-cultured with HCV-conditioned CD33+ PBMCs produced lower amounts of IFN-γ, with no effect on granzyme B production or cell viability. Importantly, this suppression of NK cell-derived IFN-γ production was mediated by CD33+CD11bloHLA-DRlo myeloid derived suppressor cells (MDSCs) via an arginase-1-dependent inhibition of mTOR activation. Suppression of IFN-γ production was reversed by L-arginine supplementation, consistent with increased MDSC arginase-1 activity. These novel results identify the induction of MDSCs in HCV infection as a potent immune evasion strategy that suppresses anti-viral NK cell responses, further indicating that blockade of MDSCs may be a potential therapeutic approach to ameliorate chronic viral infections in the liver.

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“…Дефіцит аргініну також впли ває на імунні функції клітини, в основному на пухлино інфільтровані лімфоцити, такі як цитотоксичні Тклітини, макрофаги, природні кілери (nKклітини) і дендритні клі тини (ДК). Через низьку доступність аргініну в пухлинах ці клітини виявляються функціонально нерозвинутими в пухлинних тканинах [15][16][17][18]. Ця амінокислота має по двійну роль: як імуномодулятор і бере непряму участь у прогресії пухлини через nOутворення, про що свідчать дослідження раку товстої кишки та інших видів раку.…”

Section: аргінінunclassified

Influence of immunological nutrition on treatment of patients with oncological profile

Катриченко

Lisnyi

2018

prmd

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In the reviewed article, we consider epidemiological and laboratory data that confirm the protective effects of biologically active nutrients in our diet for various diseases. Along with various factors such as alcohol, smoking, nutrition plays a vital role in influencing the patient’s immune response by transforming cells or by preventing, or acceleration of malignancy. Many data suggest that immunoactive nutrients control inflammatory and precancerous reactions in immune cells. Immunoprophylaxis is usually associated with modulation of the immune response when inflamed, thereby improving clinical outcomes. Different nutrients, including glutamine, arginine, vitamins, minerals and long-chain fatty acids, are important components of immunological nutrition. Clinical studies associated with these substances show different results with minimal effect. However, some studies have shown that these nutrients may have immunomodulatory effects that can reduce the risk of developing cancer. Pre-clinical studies claim that most of these nutrients have a positive effect in the complex treatment of cancer patients. In this article, we will consider the effect of the above nutrients on the immune system in patients of oncologic profile. Recent evidences suggest that immunological nutrition plays an important role in the development of cancer and its progression. Data from animal studies have clearly shown that the use of immunomodulatory nutrients isolated from food, by launching a cascade of immunological reactions, can detect and eliminate the tumor. Although the technology has evolved to such an extent that we can study each individual cytokine or function of the immune cell, it is difficult to demonstrate the powerful role of the immune system in preventing or treating cancer due to the complexity of the tumor cell or heterogeneity in different patients' populations. However, the study sheds light on interactions in immune responses and cancer development, prevention and therapeutic strategies that involve modulation through biologically active agents.

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Altered functions of natural killer cells in response to L-Arginine availability

Cited by 75 publications

References 45 publications

Leptin induces ROS via NOX5 in healthy and neoplastic mammary epithelial cells

Leptin induces ROS via NOX5 in healthy and neoplastic mammary epithelial cells

Hepatitis C Virus–Induced Myeloid-Derived Suppressor Cells Suppress NK Cell IFN-γ Production by Altering Cellular Metabolism via Arginase-1

Influence of immunological nutrition on treatment of patients with oncological profile

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