Sildenafil does not affect the proliferation of human lymphocytes in the in vitro transplant model

Kaleta, Beata; Boguska, Agnieszka

doi:10.18388/abp.2018_2646

Cited by 2 publications

(2 citation statements)

References 19 publications

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“…Result of current experiment corresponds to our previous findings of downregulating NK cells activity by SC [8]. Kaleta and Boguska reported that SC did not influence T cell 3 Journal of Immunology Research proliferation and had no cytotoxic effect on T cells which is in line with our observations [21]. Researchers in opposite to our findings show that cultures of lymphocytes of healthy men treated with sildenafil citrate have an increased level of TNF-α in supernatants collected from PBMC culture [22].…”

Section: Discussionsupporting

confidence: 92%

Sildenafil Citrate Influences Production of TNF-α in Healthy Men Lymphocytes

Zych

Roszczyk

Kniotek

et al. 2019

Journal of Immunology Research

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The aim of our study was to determine whether sildenafil citrate influences the production of Th1- (TNF-α, INF-γ) or Th2-type (TGF-β, IL-10) cytokines by lymphocytes of healthy men. Sildenafil citrate (SC) is a selective blocker of phosphodiesterase 5, by competing for the binding site with cGMP. It was reported that a higher risk of sexually transmitted diseases (STD) could be correlated with a recreational use of sildenafil, especially when combined with another drug. While behavioral causes of these findings are understood, it is worth considering other causes of that phenomenon that might rely on the influence of sildenafil on the immune system. Material and Methods. Peripheral blood mononuclear cells (PBMCs) were isolated from 27 healthy men donors and cultured in the presence of SC at a concentration of 400 ng/ml. The first set of research was performed on cells stimulated, for at least 4 hours, by incubation with phorbol myristate acetate (PMA), ionomycin, and Golgi-Stop. Subsequently, we determined cytokine production in cells stimulated with phytohemagglutinin (PHA) for 12 hours in the presence of Golgi-Stop. Flow cytometry immunophenotyping of PBMC was performed towards the surface marker of T cells: CD3 and intracellular cytokine expression: TNF-α, IFN-γ, TGF-β, and IL-10. Our findings show that SC significantly decreased the percentage of T cells producing TNF-α and displayed tendency to decrease IFN-γ, when stimulated with PMA. Frequent usage of SC might strengthen this effect. That could partially explain the impaired immune response to the pathogens of men using the drug.

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Section: Discussionsupporting

confidence: 92%

Sildenafil Citrate Influences Production of TNF-α in Healthy Men Lymphocytes

Zych

Roszczyk

Kniotek

et al. 2019

Journal of Immunology Research

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“…Zhu et al reported that PDE5 played a dominant role in regulating cGMP transitions that inhibited cell growth and controlled the susceptibility to apoptosis in the pulmonary endothelium [ 56 ]. Nevertheless, our specific flow cytometry analysis revealed that the drug did not affect idNK cell apoptosis, at neither early nor late stages, which confirmed the previous research results obtained by our group [ 57 , 58 ].…”

Section: Discussionsupporting

confidence: 92%

Differences in the Expression of KIR, ILT Inhibitory Receptors, and VEGF Production in the Induced Decidual NK Cell Cultures of Fertile and RPL Women

Kniotek

Roszczyk

Zych

et al. 2021

BioMed Research International

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Problem. Natural killer (NK) cells are the most abundant leukocyte population in the uterus. The interactions of the maternal NK expression of killer cell immunoglobulin-like receptors (KIRs) and human inhibitory receptor Ig-like transcript (ILT) with fetal HLA determine the activation of NK cells and pregnancy outcomes. Moreover, dNK cells release numerous angiogenic factors including VEGF. Our previous study showed that sildenafil citrate (SC) significantly decreased peripheral blood NK (pbNK) cell activity and improved intrauterine blood flow, which correlated with a successful pregnancy outcome. Thus, in this study, we investigated whether SC influenced the expression of KIR or ILT receptors on induced decidual NK (idNK), the apoptosis of cells, and VEGF-A production in the culture supernatants of idNK cells. Method of Study. pbNK cells from 24 healthy women and 23 women with RPL were converted to idNK cells under hypoxia, IL-15, and TGF-β conditions. The cultures were prepared with or without SC. Changes in KIR2DL1 (CD158a), NKG2A (CD159a), ILT-2 (CD85j), and ILT-4 (CD85d) expression on CD56+CD16- cells and their apoptosis were determined via flow cytometry. VEGF-A level was established in culture supernatants with the ELISA method. Results. KIR2DL1 and ILT-2 expression on idNK cells was higher in healthy women than in RPL patients. Sildenafil enhanced NKG2A expression in RPL patients. VEGF concentration was higher in fertile woman idNK cell cultures. idNK cells were more sensitive for necrosis in RPL than in fertile women. SC did not influence VEGF production or idNK cell apoptosis. Conclusions. A combination of hypoxia, IL-15, and AZA promotes the conversion of pbNK into idNK cells CD56+CD16--expressing KIR receptors and produces VEGF. Alterations in KIR2DL1 and ILT-2 expression as well as impaired VEGF production were associated with RPL. SC affects NKG2A expression on RPL idNK cells. SC had no effect on VEGF release or idNK cell apoptosis.

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Sildenafil does not affect the proliferation of human lymphocytes in the in vitro transplant model

Cited by 2 publications

References 19 publications

Sildenafil Citrate Influences Production of TNF-α in Healthy Men Lymphocytes

Sildenafil Citrate Influences Production of TNF-α in Healthy Men Lymphocytes

Differences in the Expression of KIR, ILT Inhibitory Receptors, and VEGF Production in the Induced Decidual NK Cell Cultures of Fertile and RPL Women

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