Mesenchymal stem cells protect from acute liver injury by attenuating hepatotoxicity of liver natural killer T cells in an inducible nitric oxide synthase‐ and indoleamine 2,3‐dioxygenase‐dependent manner

2017 ◽  
Vol 12 (2) ◽  
Author(s):  
Marina Gazdic ◽  
Bojana Simovic Markovic ◽  
Ljubica Vucicevic ◽  
Tamara Nikolic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Acute Liver Injury ◽  
Natural Killer T Cells ◽  
Dependent Manner ◽  
Oxide Synthase ◽  
Killer T Cells ◽  
Inducible Nitric Oxide

Mesenchymal stem cells attenuate acute liver injury by altering ratio between interleukin 17 producing and regulatory natural killer T cells

2017 ◽  
Vol 23 (8) ◽  
pp. 1040-1050 ◽  
Author(s):  
Neda Milosavljevic ◽  
Marina Gazdic ◽  
Bojana Simovic Markovic ◽  
Aleksandar Arsenijevic ◽  
Jasmin Nurkovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Injury ◽  
Natural Killer ◽  
Acute Liver Injury ◽  
Natural Killer T Cells ◽  
Interleukin 17 ◽  
Killer T Cells ◽  
Natural Killer T

scholarly journals Reciprocal Interactions Between Human Mesenchymal Stem Cells and γδ T Cells Or Invariant Natural Killer T Cells

Stem Cells ◽  
2009 ◽  
Vol 27 (3) ◽  
pp. 693-702 ◽  
Author(s):  
Ignazia Prigione ◽  
Federica Benvenuto ◽  
Paola Bocca ◽  
Luca Battistini ◽  
Antonio Uccelli ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Natural Killer ◽  
Human Mesenchymal Stem Cells ◽  
Γδ T Cells ◽  
Natural Killer T Cells ◽  
Reciprocal Interactions ◽  
Killer T Cells ◽  
Invariant Natural Killer

scholarly journals Mesenchymal Stem Cells Attenuate Acute Liver Failure by Promoting Expansion of Regulatory T Cells in an Indoleamine 2,3-Dioxygenase-dependent Manner

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Dragana Miloradovic ◽  
Dragica Miloradovic ◽  
Marina Gazdic Jankovic ◽  
Bojana Simovic Markovic ◽  
C. Randall Harrell ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Specific Inhibitor ◽  
Dependent Manner ◽  
Regulatory Cells ◽  
Biochemical Tests ◽  
Indoleamine 2,3 Dioxygenase

Abstract The influence of mesenchymal stem cells (MSCs) on the phenotype and function of CD4+CD49b+FoxP3- regulatory cells has not been elucidated. We used Concanavalin A (ConA) - and α-galactosylceramide (α-GalCer)-induced acute liver injury to estimate the effects of MSCs on liver-infiltrating CD4+CD49b+FoxP3-regulatory cells. MSCs significantly reduced ConA- and α-GalCer-mediated liver injury in C57BL/6 mice, as demonstrated by biochemical tests, reduced influx of inflammatory CD4+ T cells, and increased presence of CD4+CD49b+FoxP3- regulatory cells in the injured livers. The number of CD4+CD49b+FoxP3- regulatory cells was also significantly increased in α-GalCer-treated mice that received MSC-derived conditioned medium (MSC-CM). The presence of 1-methyltryptophan, a specific inhibitor of indoleamine 2,3-dioxygenase (IDO), in MSC-CM completely abrogated the hepatoprotective effect of MSCs and significantly decreased the total number of liver-infiltrated CD4+CD49b+FoxP3- regulatory cells, indicating the crucial importance of MSC-derived IDO for the expansion of CD4+CD49b+FoxP3- regulatory cells and the consequent MSC-dependent attenuation of acute liver injury.

Suppressive effects of sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on the production of NO and ROS in LPS-stimulated RAW264.7 cells

2020 ◽  
Vol 85 (4) ◽  
pp. 882-889
Author(s):  
Yan Liang ◽  
Shijiao Zha ◽  
Masanobu Tentaku ◽  
Takasi Okimura ◽  
Zedong Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ascophyllum Nodosum ◽  
Sulfated Polysaccharide ◽  
Intracellular Reactive Oxygen Species ◽  
Raw264.7 Cells ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Oxide Synthase ◽  
Dose Dependent ◽  
Inducible Nitric Oxide

ABSTRACT In this study, we found that a sulfated polysaccharide isolated from the brown alga Ascophyllum nodosum, ascophyllan, showed suppressive effects on stimulated RAW264.7 cells. Ascophyllan significantly inhibited expression of inducible nitric oxide synthase mRNA and excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner without affecting the viability of RAW264.7 cells. Ascophyllan also reduced the elevated level of intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells. Furthermore, preincubation with ascophyllan resulted in concentration-dependent decrease in ROS production in phorbol 12-myristate-13-acetate-stimulated RAW264.7 cells. Our results suggest that ascophyllan can exhibit anti-inflammatory effects on stimulated macrophages mainly through the attenuation of NO and ROS productions.

scholarly journals Activation of Nuclear Factor κB and Induction of Inducible Nitric Oxide Synthase by Ureaplasma urealyticumin Macrophages

2000 ◽  
Vol 68 (12) ◽  
pp. 7087-7093 ◽  
Author(s):  
Y.-H. Li ◽  
Z.-Q. Yan ◽  
J. Skov Jensen ◽  
K. Tullus ◽  
A. Brauner
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Alveolar Macrophages ◽  
Nuclear Factor Κb ◽  
Inos Expression ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≥4 × 107 color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone (10−4 to 10−6 M) (P < 0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids.U. urealyticum antigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response againstU. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.

scholarly journals Osteogenic Effect of Inducible Nitric Oxide Synthase (iNOS)-Loaded Mineralized Nanoparticles on Embryonic Stem Cells

2018 ◽  
Vol 51 (2) ◽  
pp. 746-762 ◽  
Author(s):  
Jin-Sun Lee ◽  
Hong Jae Lee ◽  
Jae Won Lee ◽  
Sang Cheon  Lee ◽  
Jung Sun Heo
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Nitric Oxide Synthase ◽  
Cell Viability ◽  
Osteogenic Differentiation ◽  
Inducible Nitric Oxide Synthase ◽  
Embryonic Stem ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background/Aims: This study investigated the effect of inducible nitric oxide synthase-loaded mineralized nanoparticles (iNOS-MNPs) on the osteogenic differentiation of mouse embryonic stem cells (ESCs). Methods: We prepared iNOS-MNPs using an anionic block copolymer template-mediated calcium carbonate (CaCO3) mineralization process in the presence of iNOS. iNOS-MNPs were spherical and had a narrow size distribution. iNOS was stably loaded within MNPs without denaturation. In order to confirm the successful introduction of iNOS-MNPs into the cytosol of ESCs, intracellular levels of nitric oxide (NO) was determined with a fluorometric analysis. A NO effector molecule, cyclic guanosine 3’,5’ monophosphate (cGMP) was also quantified with a competitive enzyme immunoassay. Cell viability in response to iNOS-MNP treatment was determined using the cell counting kit-8 (CCK-8) assay. Alkaline phosphatase (ALP) activity assay, intracellular calcium quantification assay, and Alizarin red S staining for matrix mineralization were performed to investigate osteogenic differentiation of ESCs. The protein levels of Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osterix (OSX) as osteogenic-related factors were also assessed by immunofluorescence staining and Western blot analysis. The complex pathways associated with iNOS-MNP-derived osteogenic differentiation of ESCs were evaluated by network-based analysis. Results: Cells with iNOS-MNPs displayed a significant increase in NO and cGMP concentration compared with the control group. When cells were exposed to iNOS-MNPs, there were no adverse effects on cell viability. Importantly, iNOS-MNP uptake promoted the osteogenic differentiation of ESCs. Using transcriptome profiling, we obtained 1,836 differentially-induced genes and performed functional enrichment analysis with ClueGO and KEGG. These analyses identified significantly enriched and interconnected molecular pathways such as protein kinase activity, estrogen receptor activity, bone morphogenetic protein (BMP) receptor binding, ligand-gated ion channel activity, and phosphatidylinositol 3-phosphate binding. Conclusion: These findings suggest that iNOS-MNPs can induce osteogenic differentiation in ESCs by integrating complex signaling pathways.

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