The Journal of pharmacy and pharmacology · 2011
Azithromycin suppresses proliferation, interleukin production and mitogen-activated protein kinases in human peripheral-blood mononuclear cells stimulated with bacterial superantigen.
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Hiwatashi Yoko, Maeda Masaki, Fukushima Hisayo, Onda Kenji, Tanaka Sachiko, Utsumi Hiroya, Hirano Toshihiko
Аннотация
OBJECTIVES: Macrolide antibiotics are used for the treatment of immunological disorders such as psoriasis. However, few studies have investigated the immunoregulatory efficacy of macrolides in bacterial superantigen-stimulated immune cells.
METHODS: The suppressive efficacies of azithromycin, clarithromycin, roxithromycin and prednisolone were evaluated in vitro against the concanavalin A- or toxic shock syndrome toxin 1 (TSST-1)-induced proliferation of peripheral-blood mononuclear cells (PBMCs) obtained from nine healthy subjects. The concentrations of six cytokines in a PBMC-culture medium were measured using bead-array procedures followed by flow cytometry. Cellular c-jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activity were measured using cell-based ELISA procedures.
KEY FINDINGS: Azithromycin, clarithromycin and roxithromycin inhibited the proliferation of both the concanavalin A- and superantigen-stimulated PBMCs dose-dependently. The effect of azithromycin was the strongest, with IC50 values of less than 5 µg/ml. Furthermore, the suppressive efficacy of prednisolone against concanavalin A- or TSST-1-stimulated PBMCs was significantly promoted in combination with 5 µg/ml azithromycin (P < 0.002). The concentrations of TNF-α, interleukin (IL)-2, -4, -5 and -10 in the supernatant of concanavalin A- or TSST-1-stimulated PBMCs cultured for 72 h decreased by 65-98% in the presence of 5 µg/ml azithromycin. The stimulation of PBMCs with concanavalin A or TSST-1 increased cellular JNK and ERK activity, and 5 µg/ml azithromycin significantly attenuated the increased activity of JNK in the TSST-1-stimulated cells and ERK in the concanavalin A- and TSST-1-stimulated PBMCs, respectively (P < 0.05).
CONCLUSIONS: Azithromycin suppresses mitogen- or superantigen-induced proliferation of PBMCs by possibly inhibiting both cellular JNK and ERK activity.
METHODS: The suppressive efficacies of azithromycin, clarithromycin, roxithromycin and prednisolone were evaluated in vitro against the concanavalin A- or toxic shock syndrome toxin 1 (TSST-1)-induced proliferation of peripheral-blood mononuclear cells (PBMCs) obtained from nine healthy subjects. The concentrations of six cytokines in a PBMC-culture medium were measured using bead-array procedures followed by flow cytometry. Cellular c-jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activity were measured using cell-based ELISA procedures.
KEY FINDINGS: Azithromycin, clarithromycin and roxithromycin inhibited the proliferation of both the concanavalin A- and superantigen-stimulated PBMCs dose-dependently. The effect of azithromycin was the strongest, with IC50 values of less than 5 µg/ml. Furthermore, the suppressive efficacy of prednisolone against concanavalin A- or TSST-1-stimulated PBMCs was significantly promoted in combination with 5 µg/ml azithromycin (P < 0.002). The concentrations of TNF-α, interleukin (IL)-2, -4, -5 and -10 in the supernatant of concanavalin A- or TSST-1-stimulated PBMCs cultured for 72 h decreased by 65-98% in the presence of 5 µg/ml azithromycin. The stimulation of PBMCs with concanavalin A or TSST-1 increased cellular JNK and ERK activity, and 5 µg/ml azithromycin significantly attenuated the increased activity of JNK in the TSST-1-stimulated cells and ERK in the concanavalin A- and TSST-1-stimulated PBMCs, respectively (P < 0.05).
CONCLUSIONS: Azithromycin suppresses mitogen- or superantigen-induced proliferation of PBMCs by possibly inhibiting both cellular JNK and ERK activity.
Предметные рубрики MeSH
AdolescentAdultAnti-Bacterial AgentsAzithromycinBacteriaCell LineCell ProliferationConcanavalin ADose-Response Relationship, DrugEnterotoxinsExtracellular Signal-Regulated MAP KinasesFemaleHumansInhibitory Concentration 50InterleukinsJNK Mitogen-Activated Protein KinasesLeukocytes, MononuclearMaleMitogen-Activated Protein KinasesPeptide FragmentsPrednisoloneSuperantigensTumor Necrosis Factor-alphaYoung Adult