Campbell V, Lynch M A
Department of Physiology, Trinity College, Dublin, Ireland.
Neuroreport. 1998 Jun 22;9(9):1923-7. doi: 10.1097/00001756-199806220-00002.
The modulation of intracellular Ca2+ concentration ([Ca2+]i) by the pro-inflammatory cytokine interleukin-1beta (IL-1beta) was assessed in synaptosomes loaded with the Ca2+-sensitive dye, Fura-2AM. IL-1beta was found to exert a biphasic effect on the KCl-induced rise in [Ca2+]i, extending an inhibitory effect at lower (3.5 ng/ml) concentrations, and a stimulatory effect at high (100 ng/ml) concentrations. The inhibitory action of IL-1beta on [Ca2+]i was sensitive to pertussis toxin (PTX; 2 microg/ml), indicating a role for a PTX-sensitive G-protein, but was unaffected by the p42 mitogen-activated protein kinase kinase (MAP kinase kinase) inhibitor, PD 098059 (2 microM). In contrast, the stimulatory action of higher concentrations of IL-1beta on [Ca2+]i was blocked by PD 098059 and unaffected by PTX. We conclude that the biphasic actions of IL-1beta on the KCl-induced rise in [Ca2+]i are mediated through activation of alternative second messenger pathways.
利用负载钙敏染料Fura-2AM的突触体评估促炎细胞因子白细胞介素-1β（IL-1β）对细胞内Ca2+浓度（[Ca2+]i）的调节作用。发现IL-1β对KCl诱导的[Ca2+]i升高具有双相作用，在较低浓度（3.5 ng/ml）时具有抑制作用，在高浓度（100 ng/ml）时具有刺激作用。IL-1β对[Ca2+]i的抑制作用对百日咳毒素（PTX；2 μg/ml）敏感，表明PTX敏感的G蛋白发挥了作用，但不受p42丝裂原活化蛋白激酶激酶（MAP激酶激酶）抑制剂PD 098059（2 μM）的影响。相反，较高浓度的IL-1β对[Ca2+]i的刺激作用被PD 098059阻断，且不受PTX影响。我们得出结论，IL-1β对KCl诱导的[Ca2+]i升高的双相作用是通过激活替代性第二信使途径介导的。
