Effect of kanglemycin C on lymphocyte proliferation induced by tetradecanoylphorbol acetate and ionomycin.

AIM: To compare the suppressions of kanglemycin C (Kan) with that of cyclosporine (Cyc) on lymphocyte proliferations induced by tetradecanoylphorbol acetate (TPA) with ionomycin (IM), and concanavalin A (Con A). METHODS: Cell proliferation was quantified with 3-(4, 5-dimetyl-thiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) or [3H]thymidine ([3H]TdR) incorporating method. Calcineurin (CN) activity was measured with molybdate dye colorimetry. RESULTS: Kan (8, 40, 80, and 400 nmol.L-1) strongly suppressed splenocyte proliferation induced by TPA and IM, and the suppressive effect of Kan gradually decreased along with the increasing concentrations of TPA (1-100 micrograms.L-1) and IM (125-500 micrograms.L-1). But, the suppression of Cyc on the splenocyte proliferation induced by TPA was mild. Cyc suppressed CN activity of mouse splenocytes stimulated by Con A stronger than Kan. Moreover, Kan and Cyc strongly suppressed spleen enriched T-cell proliferation induced by Con A and TPA + IM, and the suppression of Kan on proliferation was partly attenuated by exogenous IL-2. CONCLUSION: Kan competitively suppressed the proliferation induced by TPA and IM, and Cyc mainly suppressed IM part of the proliferation induced by TPA and IM.