In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges.
(3 S,14 S)-Petrocortyne A, a lipid compound (a C(46) polyacetylenic alcohol), from marine sponges ( Petrosia sp.) is potently cytotoxic against several solid tumour cells. In this study, we investigated in vitro anti-inflammatory and pro-aggregative effects of petrocortyne A at non-cytotoxic concentrations on various cellular inflammatory phenomena using the macrophage and monocytic cell lines RAW264.7 and U937. Petrocortyne A blocked tumour necrosis factor-alpha (TNF-alpha) production strongly and concentration-dependently in lipopolysaccharide (LPS)-activated RAW264.7 cells and phorbol 12-myristate 13-acetate (PMA)/LPS-treated U937 cells. It also blocked NO production concentration-dependently in LPS- or interferon (IFN)-gamma-treated RAW264.7 cells. Among the migration factors tested, the compound selectively blocked the expression of hepatocyte growth factor/scatter factor (HGF/SF). On the other hand, as assessed by a cell-cell adhesion assay, petrocortyne A did not block the activation of adhesion molecules induced by aggregative antibodies to adhesion molecules, but suppressed PMA-induced cell-cell adhesion significantly. Intriguingly, petrocortyne A induced U937 homotypic aggregation following long exposure (2 and 3 days), accompanied by weak induction of pro-aggregative signals such as tyrosine phosphorylation of p132 and phosphorylation of extracellular signal-related kinase 1 and 2 (ERK 1/2). Petrocortyne A may thus inhibit cellular inflammatory processes and immune cell migration to inflamed tissue.
Hong
Sungyoul
S
Department of Genetic Engineering, Sungkyunkwan University, 440-746, Suwon, South Korea.
Kim
Sung Hwan
SH
Rhee
Man Hee
MH
Kim
Ae Ra
AR
Jung
Jee H
JH
Chun
Taehoon
T
Yoo
Eun Sook
ES
Cho
Jae Youl
JY
D000114:Acetylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005233:Fatty Alcohols / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D053279:Polyynes; D011161:Porifera / Q000737:chemistry*; D011994:Recombinant Proteins; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D020298:U937 Cells
D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D005233:Fatty Alcohols; D008070:Lipopolysaccharides; D011108:Polymers; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C487015:petrocortyne A; D053279:Polyynes; D009569:Nitric Oxide; D017228:Hepatocyte Growth Factor; D007335:Insulin-Like Growth Factor II; D007371:Interferon-gamma; D019833:Genistein; D020928:Mitogen-Activated Protein Kinases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D000114:Acetylene