Open AccessThe role of inositol lipids in the activation of monocytes by interleukin‐1 and bacterial endotoxin
Author(s) -
Rotondo D.,
Earl C.R.A.,
McIntosh G.,
McIntosh F.S.,
Hepburn A.,
Milton A.S.,
Davidson J.
Publication year - 1992
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.1992.tb05909.x
Subject(s) - phosphatidylinositol , chemistry , inositol , lipopolysaccharide , eicosanoid , inositol phosphate , cytosol , biochemistry , endocrinology , biology , arachidonic acid , signal transduction , receptor , enzyme
The effect of interleukin‐1 (IL‐1) and bacterial endotoxin (lipopolysaccharide, LPS) on the activation of phosphoinositidase C (PIC) and on prostaglandin E 2 release was studied in monocytes (M?). Both IL‐1α and IL‐1β increased the release of PGE 2 in a concentration‐dependent manner, with EC 50 s of 0.48 nM and 0.12 nM, respectively. Intact M? were prelabelled with [ 3 H]inositol and the formation of inositol phosphates (IPs) was estimated by ion exchange chromatography. PIC activity was estimated directly by measuring the conversion of [ 3 H]phosphatidylinositol‐4,5,‐bisphosphate to aqueous soluble radioactivity by M? homogenates. IL‐1α (5.8 nM) increased the accumulation of IPs within 1–4 minutes and increases in IP 3 and IP 4 occured before the increase in IP 1+2 whereas LPS only increased the IPs level after at least 30 min. IL‐1α increased PIC activity in M? homogenates within 15 min with an EC 50 of 0.58 nM and IL‐1β (0.1 nM) also increased activity. Neither IL‐1α nor IL‐1β 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?.