Inhibition of lipopolysaccharide activity by a bacterial cyclic lipopeptide surfactin

Taichi Takahashi, Osamu Ohno, Yoko Ikeda, Ryuichi Sawa, Yoshiko Homma, Masayuki Igarashi, Kazuo Umezawa

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Compounds that inactivate lipopolysaccharide (LPS) activity have the potential of being new anti-inflammatory agents. Therefore, we searched among microbial secondary metabolites for compounds that inhibited LPS-stimulated adhesion between human umbilical vein endothelial cells (HUVEC) and HL-60 cells. By this screening, we found a cyclic lipopeptide surfactin from the culture broth of Bacillus sp. BML752-121F2 to be inhibitory. The addition of the surfactin prior to the LPS stimulation decreased HL-60 cell-HUVEC adhesion without showing any cytotoxicity. We confirmed that surfactin inhibited LPS-induced expression of ICAM-1 and VCAM-1 in HUVEC. It also inhibited the cellular adhesion induced by lipid A, the active component of LPS; but it did not inhibit TNF-α or IL-1β-induced cell adhesion. Then, surfactin was shown to suppress the interaction of lipid A with LPS-binding protein (LBP) that mediates the transport of LPS to its receptors. Finally, surface plasmon resonance (SPR) analysis revealed the surfactin to interact reversibly with lipid A. Thus, this Bacillus surfactin was shown to be an inhibitor of LPS-induced signal transduction, directly interacting with LPS.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalJournal of Antibiotics
Volume59
Issue number1
DOIs
Publication statusPublished - 2006 Jan

Keywords

  • Adhesion
  • HL-60 cells
  • Human umbilical vein endothelial cells
  • Lipid A
  • Lipopolysaccharide
  • Surfactin

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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