The role of inositol lipids in the activation of monocytes by interleukin-1 and bacterial endotoxin.
The effect of interleukin-1 (IL-1) and bacterial endotoxin (lipopolysaccharide, LPS) on the activation of phosphoinositidase C (PIC) and on prostaglandin E2 release was studied in monocytes (M phi). Both IL-1 alpha and IL-1 beta increased the release of PGE2 in a concentration-dependent manner, with EC50s of 0.48 nM and 0.12 nM, respectively. Intact M phi were prelabelled with [3H]inositol and the formation of inositol phosphates (IPs) was estimated by ion exchange chromatography. PIC activity was estimated directly by measuring the conversion of [3H]phosphatidylinositol-4,5-bisphosphate to aqueous soluble radioactivity by M phi homogenates. IL-1 alpha (5.8 nM) increased the accumulation of IPs within 1-4 minutes and increases in IP3 and IP4 occurred before the increase in IP1+2 whereas LPS only increased the IPs level after at least 30 min. IL-1 alpha increased PIC activity in M phi homogenates within 15 min with an EC50 of 0.58 nM and IL-1 beta (0.1 nM) also increased activity. Neither IL-1 alpha nor IL-1 beta affected the PIC activity of membrane or cytosolic fractions. LPS decreased activity in all fractions. These data indicate that IL-1, but not LPS, can directly lead to an increased activity of PIC which may be involved in eicosanoid formation in M phi.
Rotondo
D
D
Lipid Biology Unit, Rowett Research Institute, Bucksburn, Aberdeen, UK.
Earl
C R
CR
McIntosh
G
G
McIntosh
F S
FS
Hepburn
A
A
Milton
A S
AS
Davidson
J
J
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011817:Rabbits
D007295:Inositol Phosphates; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016718:Arachidonic Acid; D000841:Anisomycin; D010727:Phosphoric Diester Hydrolases; C021491:glycerophosphoinositol glycerophosphodiesterase; D015232:Dinoprostone; D002118:Calcium