6533b82afe1ef96bd128c110

RESEARCH PRODUCT

Cacospongionolide B suppresses the expression of inflammatory enzymes and tumour necrosis factor-αby inhibiting nuclear factor-κB activation

subject

description

The marine product cacospongionolide B, a sesterterpene isolated from the Mediterranean sponge Fasciospongia cavernosa, is an inhibitor of secretory phospholipase A2 with anti-inflammatory properties. In this work, we have studied the mechanism of action of this compound in the inflammatory response induced by zymosan in primary cells and in the mouse air pouch. In mouse peritoneal macrophages, cacospongionolide B was able to downregulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), resulting in decreased production of NO and prostaglandin E2 (PGE2). This compound also reduced tumour necrosis factor-α (TNF-α) mRNA expression and TNF-α levels. Cacospongionolide B inhibited nuclear factor-κB (NF-κB)-DNA binding activity and the nuclear translocation of this transcription factor. Treatment of cells with cacospongionolide B impaired NF-κB inhibitory protein (IκB-α) phosphorylation and enhanced IκB-α expression. Inhibition of iNOS, COX-2 and inflammatory mediators was confirmed in the mouse air pouch. These results show that cacospongionolide B is able to control NO, PGE2 and TNF-α production in vitro and in vivo, effects likely dependent on NF-κB inhibition. British Journal of Pharmacology (2003) 138, 1571–1579. doi:10.1038/sj.bjp.0705189