Immunomodulatory effects of the pentapeptide YGSRS on human peripheral-blood mononuclear cells.

CONTEXT: The pentapeptide YGSRS is originated from coffee bean, while its pharmacological features have little been examined. OBJECTIVES: We investigated the effects of YGSRS on proliferation, cytokine production and CD4+ CD25+ Foxp3+ regulatory T (Treg) cell frequency of human peripheral blood mononuclear cells (PBMCs) activated by T-cell mitogen. MATERIALS AND METHODS: The effects of YGSRS on T-cell mitogen-activated PBMCs were assessed by WST assay procedures. Concentrations of Th1/Th2/Th17 cytokines in the PBMCs culture medium were analyzed with beads-array procedures followed by analysis with flow cytometry. The CD4+ CD25+ Foxp3+ Treg cells in mitogen-activated PBMCs were stained with fluorescence-labeled specific antibodies followed by flow cytometry. RESULTS: YGSRS at 1-10,000 ng/ml (1.56-15,600 nM) has a tendency to promote the mitogen-activated proliferation of PBMCs, but the effects were not statistically significant. YGSRS affect the production of tumor necrosis factor (TNF) α, interleukin (IL)-4, IL-6 and IL-10 from the activated PBMCs, and statistically significant increase in the concentrations of IL-6 and IL-10 in the medium were observed at 1-1000 ng/ml (1.56-1560 nM) (p < 0.05). YGSRS has a tendency to decrease the frequency of Treg cells in the activated PBMCs, but the difference was not statistically significant. DISCUSSION AND CONCLUSIONS: The data suggest that the pentapeptide YGSRS affects the production of several types of cytokines from activated human peripheral T cells, which may modulate Th2 type immunity.

Effects of vitamin K3 and K5 on proliferation, cytokine production, and regulatory T cell-frequency in human peripheral-blood mononuclear cells.

AIMS: The effects of vitamin K (VK) derivatives VK3 and VK5 on human immune cells have not been extensively investigated. We examined the effects of VK3 and VK5 on proliferation, apoptosis, cytokine production, and CD4+CD25+Foxp3+ regulatory T (Treg) cell-frequency in human peripheral blood mononuclear cells (PBMCs) activated by T cell mitogen in vitro. MAIN METHODS: Anti-proliferative effects of VK3 and VK5 on T-cell mitogen activated PBMCs were assessed by WST assay procedures. Apoptotic cells were determined as Annexin V positive/propidium iodide (PI) negative cells. Cytokine concentrations in the supernatant of the culture medium were measured with bead-array procedures followed by analysis with flow cytometry. The CD4+CD25+Foxp3+Treg cells in mitogen-activated PBMCs were stained with fluorescence-labeled specific antibodies followed by flow cytometry. KEY FINDINGS: VK3 and VK5 suppressed the mitogen-activated proliferation of PBMCs significantly at 10-100µM (p<0.05). The data also suggest that VK3 and VK5 promote apoptosis in the mitogen-activated T cells. VK3 and VK5 significantly inhibited the production of tumor necrosis factor (TNF) α, interleukin (IL)-4, -6, and -10 from the activated PBMCs at 10-100µM (p<0.05). In contrast, VK3 and VK5 significantly increased Treg cell-frequency in the activated PBMCs at concentrations more than 10µM (p<0.001). SIGNIFICANCE: Our data suggest that VK3 and VK5 attenuate T cell mediated immunity by inhibiting the proliferative response and inducing apoptosis in activated T cells.

Suppressive effects of peptide antibiotics against proliferation and cytokine production in mitogen-activated human peripheral-blood mononuclear cells.

Certain kinds of peptide antibiotics are suggested to have immunomodulatory effects; however, few studies have been carried out systemically to evaluate the antiproliferative effects of peptide antibiotics in human lymphoid cells. The suppressive efficacies of nine peptide antibiotics and seven non-antibiotic peptides against proliferation of human peripheral-blood mononuclear cells (PBMCs) stimulated with T cell mitogen were examined in vitro. Nigericin (CAS 28643-80-3), valinomycin (CAS 2001-95-8), gramicidin D (CAS 1405-97-6), and tyrothricin (CAS 1404-88-2) strongly inhibited the proliferation of concanavalin A-stimulated PBMCs with IC50 values of 0.15-11.2 ng/ml, while these antibiotics did not show cytotoxicity at 10 000 ng/ml. The IC50 value of the immunosuppressant cyclosporine (CAS 59865-13-3) was 5.2 ng/ml. Virginiamycin (CAS 11006-76-1) and gramicidin S (CAS 113-73-5) moderately inhibited PBMC-proliferation with IC50 values of 1000 and 1900 ng/ml, respectively. On the other hand, bacitracin (CAS 1405-87-4), capreomycin (CAS 11003-38-6), polymyxin B (1404-26-8), angiotensin II antipeptide (CAS 121379-63-3), angiotensin III antipeptide (CAS 133605-55-7), fibrinogen binding inhibitor peptide (CAS 89105-94-2), LH-RH (CAS 71447-49-9), pepstatin A (CAS 26305-03-3), oxytocin (CAS 50-56-6), and vasopressin (CAS 16679-58-6) showed little or no suppressive effect on PBMC-proliferation. Nigericin and valinomycin decreased the concentrations of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, and IL-17 in the culture medium with IC50 values less than 0.01 ng/ml. Nigericin also decreased the concentrations of IL-4 and IL-6 with IC50 values of less than 1 ng/ml. The results show that peptide antibiotics such as nigericin and valinomycin efficiently suppress the production of several cytokines and proliferation in mitogen-stimulated human PBMCs.