The effect of monophosphoryl lipid A on lipopolysaccharide-induced prostaglandin E2 release in human choriodecidua.
The aim of this study was to determine the effect of an inhibitor of bacterial endotoxin, monophosphoryl lipid A (MLA), on lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) formation by human choriodecidua explants incubated in vitro. LPS induced the release of PGE2 from explants in a time-and dose-dependent manner (P < 0.05, n = 5), thus establishing the efficacy of the experimental model. MLA at concentrations of 10 micrograms/ml also increased PGE2 release from explants when compared to vehicle controls (P < 0.05, n = 5). When used at a concentration that did not stimulate PGE2 release (1 microgram/ml), MLA pretreatment, coincubation or a combination of these protocols did not significantly affect LPS-induced PGE2 release. These data establish that MLA does not act by abrogating tissue LPS responsiveness. Under the conditions utilized in this study, MLA acts locally as a low potency 'LPS-like agent'. The previously reported in vivo efficacy of systemically administered MLA may involve the partial depletion or down regulation of LPS response pathways and the subsequent development of LPS tolerance.
Nicholls
L
L
Department of Pathology and Immunology, Monash Medical School, Alfred Hospital, Prahran, Victoria, Australia.
Farrugia
W
W
Rice
G E
GE
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002823:Chorion / Q000378:metabolism*; D046508:Culture Techniques; D003656:Decidua / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011247:Pregnancy
D000276:Adjuvants, Immunologic; D008050:Lipid A; D008070:Lipopolysaccharides; D015232:Dinoprostone; C048436:monophosphoryl lipid A