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The Journal of Immunology, Vol 146, Issue 12 4222-4227, Copyright © 1991 by American Association of Immunologists
ARTICLES |
A Vazquez, MT Auffredou, P Galanaud and G Leca
INSERM U 131, Clamart, France.
The second messenger cAMP is a modulator of cellular growth possessing both inhibitory and stimulatory properties. In this report, we show that IL-2- and IL-4-dependent DNA synthesis of anti-mu-activated human B cells is modulated in opposite ways by agents increasing intracellular levels of cAMP. Forskolin and 2'-O-dibutyriladenosine- 3',5'-cyclic monophosphate had no proliferative effect by themselves. Nevertheless they decreased IL-2-driven proliferation and increased IL- 4-mediated DNA synthesis. IL-4 and cAMP each inhibited the IL-2- dependent proliferation with similar patterns of reactivity. Both IL-4 and forskolin needed to be present during the first 48 h of culture to display inhibitory activity, and preactivation of B cells for 16 h with forskolin and IL-4 did not prevent further B cell response to IL-2. This suggests that cAMP and IL-4 directly interact with IL-2 signaling. In addition, we show that the cAMP-dependent protein kinase inhibitor N- (2-methylamino-ethyl)-5-iso-quinoline-sulfamide reversed the IL-4- inhibitory effect on IL-2-driven proliferation. Our data suggest that the IL-4-inhibitory signal to IL-2-driven human B cell proliferation involves cAMP-dependent protein kinase activation.
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