INTERLEUKIN-13 INHIBITS PROTEIN-KINASE C-TRIGGERED RESPIRATORY BURST IN HUMAN MONOCYTES - ROLE OF CALCIUM AND CYCLIC-AMP

Interleukin 13 (IL-13), a novel cytokine produced by activated lymphoc ytes modulates some monocyte functions, but no data is available conce rning the signal transduction pathway. We show here, the inhibitory ef fect of IL-13 on 12-O-tetradecanoylphorbol-13-acetate (TPA)-triggered reactive oxygen intermediate production in human monocytes and the sig nals involved in this response. Our results show that IL-13 produces r apid and transient phosphoinositide hydrolysis and intracellular Ca2mobilization. Furthermore, IL-13 induces intracellular cAMP accumulati on through inositol 1,4,5-trisphosphate-dependent Ca2+ mobilization. M etabolic inhibitors were used to relate the first steps in signaling p athways to the inhibitory effect of IL-13 on TPA-triggered reactive ox ygen intermediate production. Indeed, inhibitors of phospholipase C (n eomycin), intracellular Ca2+ mobilization (8-[N,N-diethylamino]-octyl 3,4,5-trimethoxybenzoate hydrochloride), adenylate cyclase (Delta(9)-t etrahydrocannabinol), and protein kinase A (N omocinnamylamino)ethyl]- 5-isoquinolinesulfonamide) impair the IL-13 inhibitory response. Altog ether these observations indicate that modulatory effect of IL-13 on t he TPA-induced oxidative burst is the result of the intracellular cAMP accumulation through an inositol 1,4,5-trisphosphate-induced Ca2+ mob ilization-dependent pathway.