In human monocytes interleukin-1 stimulates a phospholipase C active on phosphatidylcholine and inactive on phosphatidylinositol.
Interleukin-1 (IL-1) can initiate the synthesis of prostaglandins which in turn act as endogenous modulators of IL-1 production. The human monocyte/macrophage synthesizes various eicosanoids through the activation of the cellular phospholipase system. Cell stimulation results in the activation of phospholipase A2 (PLA2) whose major substrate is phosphatidylcholine (PC) and the release of the eicosanoid precursor arachidonic acid (AA) from PC. Another pathway is the stimulation of a phospholipase C (PLC) mainly active on phosphoinositides and the resulting formation of inositol phosphates (IPs) and diacylglycerol (DAG). Phospholipids other than phosphoinositides can also be hydrolysed by PLC to give rise to DAG. Studies have shown that IL-1 does not activate the IP pathway, but it primarily stimulates a PLC linked to phosphatidylethanolamine in cultured rat mesangial cells, and a PLC linked to PC in Jurkart cells. We have stimulated human monocytes with IL-1 and calcium ionophore A23187 and we have observed their effect on the phospholipase system. The results indicate that IL-1 does not activate the formation of IPs in cells labeled with [3H]myo-inositol. In contrast, in cells labeled with [3H]AA, IL-1 causes the formation of DAG associated with the hydrolysis of PC. Moreover, after stimulation with IL-1 there is no accumulation of free AA which would indicate that there has been no activation of PLA2, which occurs instead with A23187 stimulation. These data suggest that, in monocytes, IL-1 does not directly stimulate a PLA2 or a PLC active on phosphatidylinositol; instead it primarily stimulates a PLC active on PC.
Galella
G
G
Institute of Pharmacological Sciences, University of Milan, Milano, Italy.
Medini
L
L
Stragliotto
E
E
Stefanini
P
P
Rise
P
P
Tremoli
E
E
Galli
C
C
D000001:Calcimycin / Q000494:pharmacology; D004075:Diglycerides / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010738:Type C Phospholipases / Q000378:metabolism*
D004075:Diglycerides; D005227:Fatty Acids; D007375:Interleukin-1; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D000001:Calcimycin; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases