Intracellular signaling events associated with the induction of DNA synthesis in human B lymphocytes. II. Different pathways triggered by IL-2 and IL-4.
In attempts to detect associations between early signaling events triggered by interleukins and the induction of DNA synthesis, inhibitors of various second messenger pathways were tested for their effects on IL-2- and IL-4-elicited mitogenesis in preactivated human B lymphocytes. Inhibitors of phosphoinositidase C and of InsP3-induced calcium release suppressed IL-4- but not IL-2-mediated proliferation. The response to both lymphokines was also impaired by an inhibitor of the calcium/calmodulin complex and was modulated by variations of the [Ca2+]i. PKC inhibitors and PK-C depletion did not significantly alter the response to IL-2 and IL-4. The response to IL-2, but not to IL-4, was inhibited by cAMP analogues or by agents that raise cAMP. In contrast, IL-4, but not IL-2, stimulated cAMP accumulation in activated B cells. Taken together, these observations indicate that IL-2 and IL-4 use different signaling pathways to induce the G1-->S transition in these cells and suggest that the IL-4 inhibition of the B cell response to IL-2 may result from its effect on cAMP generation.
U196 INSERM, Institut Curie, Paris, France.
J P
JP
Kolb
A
A
Abadie
N
N
Paul-Eugene
B
B
Dugas
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D009355:Neomycin / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D007376:Interleukin-2; D015847:Interleukin-4; D000001:Calcimycin; D004247:DNA; D000242:Cyclic AMP; D010738:Type C Phospholipases; D009355:Neomycin