Inhibition of lipopolysaccharide activity by a bacterial cyclic lipopeptide surfactin

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

研究成果: Article査読

28 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)35-43
ページ数9
ジャーナルJournal of Antibiotics
59
1
DOI
出版ステータスPublished - 2006 1

ASJC Scopus subject areas

  • 薬理学
  • 創薬

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