Involvement of cyclic adenosine monophosphate in the interleukin 4 inhibitory effect on interleukin 2-induced lymphokine-activated killer generation.
In previous studies, IL-4 has been reported to interfere with IL-2-driven generation of lymphokine-activated killer (LAK) activity. In this investigation, we have demonstrated that IL-4 inhibited the IL-2-induced differentiation of large granular lymphocytes (LGL) into LAK effectors by a mechanism involving, at least in part, an increase in LGL intracellular cAMP levels. In contrast, with its capacity to induce cAMP accumulation in resting LGL, IL-4 had a very negligible effect on LAK activity induction, and cAMP levels increase in LGL that had been preincubated with IL-2. Furthermore, the inhibitory effect of IL-4 on LAK activity generation also correlated with a marked decrease in N-CBZ-L-lysine thiobenzylester esterase activity, with an inhibition of tumor necrosis factor (TNF) mRNA expression and TNF production by IL-2-stimulated LGL. These results strongly suggest that complex signaling processes could be ascribed to the dual activities of cytokines and their interplay in LAK promotion.
Blay
J Y
JY
Laboratoire d'Immunologie UA1156, Institut Gustave Roussy, Villejuif, France.
Branellec
D
D
Robinet
E
E
Dugas
B
B
Gay
F
F
Chouaïb
S
S
D002454:Cell Differentiation / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology*; D004950:Esterases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D000242:Cyclic AMP; D004950:Esterases; C022635:serine esterase