scholarly journals Hambatan Mesenchymal Stem Cell Terhadap Proliferasi Limfosit T

2018 ◽  
Vol 20 (3) ◽  
pp. 212
Author(s):  
Sofia Fajarwati

AbstractMesenchymal stem cells (MSCs) are a kind of stem cells that can differentiate into several kinds of mesodermal cell decent. MSCs can be cultured in vitro therefore it can serve many purposes. However, MSCs also have immunosuppresion effects, one of the way is by suppresing T cell proliferation. MSCs need cell-to-cell contact with activated T cells in certain rasio to release it’s surppresion properties. Primery help from inflamatory cytokines is also needed. MSCs’s suppresion effect can be mediated by several molecules such as indoleamine 2,3-dioxygenase (IDO), inducible nitric-oxide synthase (iNOS), prostaglandin E2 (PGE2), transform growth factor-β (TGF-β), hepatocyte growth factor (HGF), and HLA-G5 soluble. MSCs’s characteristic and culture conditions can affect clinical applications.Keywords: Mesenchymal stem cells, T cell proliferation, immunosuppresion AbstrakMesenchymal stem cells (MSC) adalah salah satu jenis stem cell yang dapat berdiferensiasi menjadi beberapa macam turunan sel mesodermal. MSC dapat dikembangkan secara in-vitro sehingga memiliki banyak kegunaan. Namun, MSC juga dapat memberikan beberapa efek imunosupresi, salah satunya dengan cara menekan proliferasi sel T. Untuk melakukan supresi, MSC memerlukan kontak cell-to-cell dengan sel T teraktivasi dengan rasio tertentu. MSC juga membutuhkan bantuan awal dari sitokin inflamasi. Efek supresi MSC dapat diperantarai oleh beberapa molekul seperti indoleamine 2,3-dioxygenase (IDO), inducible nitric- oxide synthase (iNOS), prostaglandin E2 (PGE2), transform growth factor-β (TGF-β), hepatocyte growth factor (HGF), dan HLA-G5 terlarut. Sifat dan kondisi biakan MSC dapat mempengaruhi aplikasi klinis.Kata kunci: Mesenchymal stem cells, proliferasi sel T, imunosupresi

2007 ◽  
Vol 283 (3) ◽  
pp. 1713-1722 ◽  
Author(s):  
Dachuan Huang ◽  
Deyu Tarika Cai ◽  
Rong Yuan Ray Chua ◽  
David Michael Kemeny ◽  
Siew Heng Wong

Dendritic cells (DC) are professional antigen-presenting cells that possess specific and efficient mechanisms to initiate immune responses. Upon encounter with pathogens, immature DC will go through a maturation process that converts them to highly immunogenic mature DC. Despite the fact that nitric oxide (NO) was produced in large amounts in maturing DC, it is still unclear whether NO is the key molecule that initiates and enhances DC maturation and T cell proliferation, respectively. Here, we report that NO donor and overexpression of either nitric-oxide synthase 2 (NOS2) or nitric-oxide synthase 3 (NOS3) alone can induce surface expression of major histocompatibility complex class II (MHC II) and both the essential co-stimulatory molecules CD80 and CD86 in immature DC. Consistently, NO donor-treated immature DC were capable of enhancing T cell proliferation in vitro in the absence of lipolysaccharide. Interestingly, NOS2 interacts with CD74 (the MHC II-associated invariant chain), and the degradation of CD74 by caspases in immature DC was inhibited upon treatment with NO donor. Because the trafficking of MHC II is CD74-dependent, the increase in cell surface localization of MHC II in maturing DC is in part due to the increase in CD74 protein expression in the presence of NOS2 and NO.


2018 ◽  
Vol 60 (No. 8) ◽  
pp. 359-366
Author(s):  
J. Li ◽  
B. Shi ◽  
S. Yan ◽  
L. Jin ◽  
Y. Guo ◽  
...  

The effects of chitosan on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity and gene expression in vivo or vitro were investigated in weaned piglets. In vivo, 180 weaned piglets were assigned to five dietary treatments with six replicates. The piglets were fed on a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. In vitro, the peripheral blood mononuclear cells (PBMCs) from a weaned piglet were cultured respectively with 0 (control), 40, 80, 160, and 320 µg chitosan/ml medium. Results showed that serum NO concentrations on days 14 and 28 and iNOS activity on day 28 were quadratically improved with increasing chitosan dose (P < 0.05). The iNOS mRNA expressions were linearly or quadratically enhanced in the duodenum on day 28, and were improved quadratically in the jejunum on days 14 and 28 and in the ileum on day 28 (P < 0.01). In vitro, the NO concentrations, iNOS activity, and mRNA expression in unstimulated PBMCs were quadratically enhanced by chitosan, but the improvement of NO concentrations and iNOS activity by chitosan were markedly inhibited by N-(3-[aminomethyl] benzyl) acetamidine (1400w) (P < 0.05). Moreover, the increase of NO concentrations, iNOS activity, and mRNA expression in PBMCs induced by lipopolysaccharide (LPS) were suppressed significantly by chitosan (P < 0.05). The results indicated that the NO concentrations, iNOS activity, and mRNA expression in piglets were increased by feeding chitosan in a dose-dependent manner. In addition, chitosan improved the NO production in unstimulated PBMCs but inhibited its production in LPS-induced cells, which exerted bidirectional regulatory effects on the NO production via modulated iNOS activity and mRNA expression.


2018 ◽  
Vol 51 (2) ◽  
pp. 746-762 ◽  
Author(s):  
Jin-Sun Lee ◽  
Hong Jae Lee ◽  
Jae Won Lee ◽  
Sang Cheon  Lee ◽  
Jung Sun Heo

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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