Regulation of NK Cell Function by Human Granulocyte Arginase

Oberlies, Johanna; Watzl, Carsten; Giese, Thomas; Luckner, Claudia; Kropf, Pascale; Müller, Ingrid; Ho, Anthony D.; Munder, Markus

doi:10.4049/jimmunol.0803523

Cited by 115 publications

(94 citation statements)

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“…A similar regulation of human NK cells by arginase released from granulocytes has also been reported [31]. Furthermore, it has recently been shown that meschymal stromal cells transform neutrophils into an immunosuppressive phenotype in part by inducing arginase expression and activity [32,33].…”

Section: Discussionmentioning

confidence: 67%

Hypoxic Proliferation of Osteosarcoma Cells Depends on Arginase II

Setty

Jin

Houghton

et al. 2016

Cell Physiol Biochem

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Background/Aims: Despite significant advancements in the diagnosis and treatment of osteosarcoma, the overall survival has remained relatively unchanged for over two decades. Hypoxic conditions have been demonstrated in solid tumors and are associated with increased cell proliferation and angiogenesis. L-arginine metabolism by arginase produces L-ornithine, the precursor for polyamine and proline synthesis required for cellular proliferation. We hypothesized that hypoxia would increase cellular proliferation via arginase induction in human osteosarcoma cell lines. Methods: We utilized a variety of approaches to examine the role of arginase II in hypoxic (1% O₂, 5% CO₂) cellular proliferation. Results: Arginase II mRNA and protein levels were significantly increased in osteosarcoma cells exposed to hypoxia for 48 hours. There were twice as many viable cells following 48 hours of hypoxia than following 48 hours of normoxia (21% O₂, 5% CO₂). The addition of difluoromethylornithine (DFMO), a putative arginase inhibitor, prevented hypoxia-induced proliferation. Transfection of small interfering RNAs (siRNA) targeting arginase II resulted in knockdown of arginase II protein levels and prevented hypoxia-induced cellular proliferation. Conclusions: These data support our hypothesis that hypoxia increases proliferation of osteosarcoma cells in an arginase II-dependent manner. We speculate that arginase II may represent a therapeutic target in osteosarcoma.

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Section: Discussionmentioning

confidence: 67%

Hypoxic Proliferation of Osteosarcoma Cells Depends on Arginase II

Setty

Jin

Houghton

et al. 2016

Cell Physiol Biochem

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“…Накопичені дані свідчать про те, що існують дві грані nO: вона може діяти і як промотор пухлини, і як інгібітор пухлинних клітин [17]. Подвійна роль nO в розвитку раку залежить від його концентрації та інших супутніх чинни ків.…”

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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“…Метаболическое действие ней-ротоксичности аммиака связано с изменением уровня секреции ROS и RNS, метаболизма NO, уровня cAMP, MAPK-киназного сигнального пути, структуры цитоскелета. Токсическое дей-ствие NH 3 на клетки приводит к усилению про-дукции TNFα и IL-1β, которые в свою очередь индуцируют продукцию ROS, активацию PKA, ERK и NF-κB [8,75]. Нельзя исключать, что NH 3, генерируемый в результате активности АД, будет оказывать схожее токсическое действие на дру-гие типы клеток.…”

Section: иммуносупрессорные эффекты аргининдеиминазыunclassified