SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells
Stromal cell-derived factor-1 alpha (SDF-1α) has been shown to be up-regulated in a variety of malignancies. So that, its expression is associated with poor prognosis and invasiveness. Natural killer (NK) cells are important effector cells against virus-infected and transformed cells. Especially the...
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| Format: | Article |
| Language: | English |
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Tehran University of Medical Sciences
2019-10-01
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| Series: | Iranian Journal of Allergy, Asthma and Immunology |
| Subjects: | |
| Online Access: | https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2265 |
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| author | Alireza Mardomi Hadi Hossein-Nataj Narjes Jafari Nabiallah Mohammadi Saeid Abediankenari |
| author_facet | Alireza Mardomi Hadi Hossein-Nataj Narjes Jafari Nabiallah Mohammadi Saeid Abediankenari |
| author_sort | Alireza Mardomi |
| collection | DOAJ |
| description | Stromal cell-derived factor-1 alpha (SDF-1α) has been shown to be up-regulated in a variety of malignancies. So that, its expression is associated with poor prognosis and invasiveness. Natural killer (NK) cells are important effector cells against virus-infected and transformed cells. Especially they play a key role in tumor immune surveillance. Whereas it was not well understood whether SDF-1α modulates anti-tumor immune response or not, the purpose of the present study was to investigate the effect of SDF-1α on the cytotoxic properties of peripheral blood NK cells. Human peripheral blood NK cells were freshly isolated using MACSxpess system and cultured in the presence or absence of recombinant human SDF-1α or SDF-1α plus CXCR4 antagonist, AMD3100. CD107a degranulation assay was conducted through the co-culture of NK cells with K562 cells. The percentage of CD107a positive cells was assessed by flowcytometry. Effect of SDF-1α was also examined on the mRNA levels of NKG2A and NKG2D as indicator examples of NK cell inhibitory and activating receptors, respectively. SDF-1α significantly decreased the degranulation activity of NK cells (p=0.04). The mRNA content of NKG2D was down-regulated under the influence of SDF-1α (p=0.03). Moreover, AMD3100 exhibited a trend in recovering the NKG2D mRNA level to its un-treated state (p=0.05). The present study reveals that SDF-1α has a negative impact on NK cell activity and might is involved in tumor immune-suppression. Thus, it can be concluded that microenvironment manipulations targeting SDF-1α may reinforce current cancer therapies by disturbing one of the immune-suppressive axes in the cancerous milieu. |
| first_indexed | 2024-12-12T22:01:31Z |
| format | Article |
| id | doaj.art-eadfcb34cb4148719b93da9bd06ed623 |
| institution | Directory Open Access Journal |
| issn | 1735-1502 1735-5249 |
| language | English |
| last_indexed | 2024-12-12T22:01:31Z |
| publishDate | 2019-10-01 |
| publisher | Tehran University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Allergy, Asthma and Immunology |
| spelling | doaj.art-eadfcb34cb4148719b93da9bd06ed6232022-12-22T00:10:31ZengTehran University of Medical SciencesIranian Journal of Allergy, Asthma and Immunology1735-15021735-52492019-10-0118510.18502/ijaai.v18i5.19172265SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 CellsAlireza Mardomi0Hadi Hossein-Nataj1Narjes Jafari2Nabiallah Mohammadi3Saeid Abediankenari4Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran AND Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, IranDepartment of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, IranImmunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, IranImmunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran AND Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran AND Student Research Committee, Mazandaran University of Medical Sciences, Sari, IranImmunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran AND Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, IranStromal cell-derived factor-1 alpha (SDF-1α) has been shown to be up-regulated in a variety of malignancies. So that, its expression is associated with poor prognosis and invasiveness. Natural killer (NK) cells are important effector cells against virus-infected and transformed cells. Especially they play a key role in tumor immune surveillance. Whereas it was not well understood whether SDF-1α modulates anti-tumor immune response or not, the purpose of the present study was to investigate the effect of SDF-1α on the cytotoxic properties of peripheral blood NK cells. Human peripheral blood NK cells were freshly isolated using MACSxpess system and cultured in the presence or absence of recombinant human SDF-1α or SDF-1α plus CXCR4 antagonist, AMD3100. CD107a degranulation assay was conducted through the co-culture of NK cells with K562 cells. The percentage of CD107a positive cells was assessed by flowcytometry. Effect of SDF-1α was also examined on the mRNA levels of NKG2A and NKG2D as indicator examples of NK cell inhibitory and activating receptors, respectively. SDF-1α significantly decreased the degranulation activity of NK cells (p=0.04). The mRNA content of NKG2D was down-regulated under the influence of SDF-1α (p=0.03). Moreover, AMD3100 exhibited a trend in recovering the NKG2D mRNA level to its un-treated state (p=0.05). The present study reveals that SDF-1α has a negative impact on NK cell activity and might is involved in tumor immune-suppression. Thus, it can be concluded that microenvironment manipulations targeting SDF-1α may reinforce current cancer therapies by disturbing one of the immune-suppressive axes in the cancerous milieu.https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2265Immunologic cytotoxicityKiller cellsNaturalNKG2DSDF-1α |
| spellingShingle | Alireza Mardomi Hadi Hossein-Nataj Narjes Jafari Nabiallah Mohammadi Saeid Abediankenari SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells Iranian Journal of Allergy, Asthma and Immunology Immunologic cytotoxicity Killer cells Natural NKG2D SDF-1α |
| title | SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells |
| title_full | SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells |
| title_fullStr | SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells |
| title_full_unstemmed | SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells |
| title_short | SDF-1α Reduces Human Natural Killer Cell Cytotoxicity against Chronic Myelogenous Leukemia K562 Cells |
| title_sort | sdf 1α reduces human natural killer cell cytotoxicity against chronic myelogenous leukemia k562 cells |
| topic | Immunologic cytotoxicity Killer cells Natural NKG2D SDF-1α |
| url | https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2265 |
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