Inhibition of lipopolysaccharide activity by a bacterial cyclic lipopeptide surfactin.
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-alpha or IL-1 beta-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.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan.
Taichi
T
Takahashi
Osamu
O
Ohno
Yoko
Y
Ikeda
Ryuichi
R
Sawa
Yoshiko
Y
Homma
Masayuki
M
Igarashi
Kazuo
K
Umezawa
D001407:Bacillus / Q000737:chemistry / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D003470:Culture Media / Q000737:chemistry; D042783:Endothelial Cells / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008050:Lipid A / Q000037:antagonists & inhibitors; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D020349:Surface Plasmon Resonance; D013501:Surface-Active Agents / Q000494:pharmacology; D014343:Trypan Blue; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004396:Coloring Agents; D003470:Culture Media; D007375:Interleukin-1; D008050:Lipid A; D055666:Lipopeptides; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; D013501:Surface-Active Agents; D014409:Tumor Necrosis Factor-alpha; C009365:surfactin peptide; D014343:Trypan Blue