Isolation of heptadepsin, a novel bacterial cyclic depsipeptide that inhibits lipopolysaccharide activity.
Lipopolysaccharide (LPS) is considered to cause various inflammatory reactions. We searched among microbial secondary metabolites for compounds that could inhibit LPS-stimulated adhesion between human umbilical vein endothelial cells (HUVEC) and human myelocytic cell line HL-60 cells. In the course of our screening, we isolated a novel cyclic depsipeptide, which we named heptadepsin, from the whole culture broth of Paenibacillus sp. The addition of heptadepsin prior to LPS stimulation decreased HL-60 cell-HUVEC adhesion without showing any cytotoxicity. It also inhibited the cellular adhesion induced by lipid A, the active component of LPS, but it did not inhibit TNF-alpha or IL-1beta-induced cell adhesion. The result of surface plasmon resonance (SPR) analysis revealed that heptadepsin interacted with lipid A directly. Thus, heptadepsin, a novel naturally occurring cyclic heptadepsipeptide, was shown to inactivate LPS by direct interaction with LPS.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan.
Osamu
O
Ohno
Yoko
Y
Ikeda
Ryuichi
R
Sawa
Masayuki
M
Igarashi
Naoko
N
Kinoshita
Yoshikazu
Y
Suzuki
Kensuke
K
Miyake
Kazuo
K
Umezawa
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology* / Q000633:toxicity; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007938:Leukemia / Q000473:pathology; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4
D047630:Depsipeptides; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C496213:heptadepsin, Paenibacillus; D017239:Paclitaxel