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Immunology. 2003 Sep;110(1):66-72.

Cell activation by monosaccharide lipid A analogues utilizing Toll-like receptor 4.

Author information

1
Department of Oral Microbiology, Asahi University School of Dentistry, Gifu, Japan.

Abstract

Lipid A is the bioactive centre of lipopolysaccharide (LPS), and its properties exhibit various endotoxic and biological effects toward host cells. We examined whether Toll-like receptors (TLRs) are mediated by the signals from various synthetic acylated derivatives of d-glucosamine monophosphate. All test synthetic monosaccharide lipid A analogues similar to acylated beta-(1-6)-d-glucosamine disaccharide bisphosphates, such as Escherichia coli-type lipid A (compound 506) and its precursor (compound 406), clearly induced nuclear factor (NF)-kappaB activation in Ba/F3 cells expressing murine TLR4 and its accessory protein MD-2 (Ba/mTLR4/mMD-2), but no induction was found in those expressing murine TLR2 (Ba/mTLR2). Compound 411, the non-reducing sugar moiety of compound 506, exhibited interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha)-producing activities in human peripheral blood mononuclear cells (PBMC), whereas compound 401, the reducing moiety of compounds 506 and 406, and Gifu lipid A-46 (GLA-46), the non-reducing moiety of compound 406, induced no production of IL-8 and TNF-alpha, which was similar to the findings for compound 406. Among the synthetic triacylated monosaccharide lipid A analogues, some compounds with three tetradecanoyl (C14) groups or that included a dodecanoyl (C12) group were more active toward murine and human cells than were other analogues with a decanoyl (C10) or hexadecanoyl (C16) group. Furthermore, IL-8 production in PBMC stimulated with the active monosaccharide lipid A analogues as well as compound 506 was clearly inhibited by the monoclonal antibody to human TLR4. These findings suggest that monosaccharide lipid A analogues similar to disaccharide lipid As are capable of activating both murine and human cells through TLR4.

PMID:
12941142
PMCID:
PMC1783012
DOI:
10.1046/j.1365-2567.2003.01709.x
[Indexed for MEDLINE]
Free PMC Article

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