title: Suppressive effects of peptide antibiotics against proliferation and cytokine production in mitogen-activated human peripheral-blood mononuclear cells.
abstract: 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.
authors.affiliation: Bohsei Pharmacy, Kanagawa, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Maeda
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ishizawa
authors.forename: Yurie
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Onda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002469:Cell Separation; D002470:Cell Survival; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D009550:Nigericin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects; D014634:Valinomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D008934:Mitogens; D010455:Peptides; D014634:Valinomycin; D016572:Cyclosporine; D009550:Nigericin