In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges.

Abstract

(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.

• Authors: Sungyoul Hong, Sung Hwan Kim, Man Hee Rhee, Ae Ra Kim, Jee H Jung, Taehoon Chun, Eun Sook Yoo, Jae Youl Cho
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 368 Issue 6 Pg. 448-56 (Dec 2003) ISSN: 0028-1298 [Print] Germany
• PMID: 14615882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cell Adhesion Molecules
• Fatty Alcohols
• Lipopolysaccharides
• Polymers
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• petrocortyne A
• Polyynes
• Nitric Oxide
• Hepatocyte Growth Factor
• Insulin-Like Growth Factor II
• Interferon-gamma
• Genistein
• Mitogen-Activated Protein Kinases
• Staurosporine
• Tetradecanoylphorbol Acetate
• Acetylene

Topics

• Acetylene (analogs & derivatives, chemistry, pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Autocrine Communication (drug effects, physiology)
• Cell Adhesion Molecules (biosynthesis)
• Cell Aggregation (drug effects)
• Cell Differentiation (drug effects)
• Cell Line
• Fatty Alcohols (pharmacology)
• Genistein (pharmacology)
• Hepatocyte Growth Factor (biosynthesis)
• Humans
• Insulin-Like Growth Factor II (biosynthesis)
• Interferon-gamma (pharmacology)
• Lipopolysaccharides (pharmacology)
• Macrophages (metabolism)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• Nitric Oxide (biosynthesis)
• Phosphorylation
• Polymers (chemistry, pharmacology)
• Polyynes
• Porifera (chemistry)
• Recombinant Proteins
• Staurosporine (pharmacology)
• Tetradecanoylphorbol Acetate (pharmacology)
• Tumor Necrosis Factor-alpha (biosynthesis)
• U937 Cells