Innate immunomodulation by lipophilic termini of lipopolysaccharide; Synthesis of lipid As from Porphyromonas gingivalis and other bacteria and their immunomodulative responses

Yukari Fujimoto, Atsushi Shimoyama, Akinori Saeki, Naohiro Kitayama, Chika Kasamatsu, Hiroko Tsutsui, Koichi Fukase

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10 Citations (Scopus)

Abstract

Synthetic studies of lipid A and LPS partial structures have been performed to investigate the relationship between structures and functions of LPS. Recent studies have suggested several pathological implications of LPS from parasitic bacteria due to its influence on the host immune responses. To address this issue, we established an efficient synthetic strategy that is widely applicable to the synthesis of various lipid As by using a key disaccharide intermediate with selectively cleavable protecting groups. Porphyromonas gingivalis and Helicobacter pylori lipid As were synthesized and their biological activities were evaluated. All synthetic lipid As did not induce strong inflammatory responses: some are very weak cytokine inducers and others are antagonistic in IL-6 and IL-8 induction with E. coli LPS. On the other hand, P. gingivalis lipid As showed potent IL-18 inducing activity. Since IL-18 has been shown to correlate with chronic inflammation, P. gingivalis LPS may be implicated in the chronic inflammatory responses.

Original languageEnglish
Pages (from-to)987-996
Number of pages10
JournalMolecular BioSystems
Volume9
Issue number5
DOIs
Publication statusPublished - 2013 May 1

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ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

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