prostaglandin-d2 and n-hexane

The purpose of this study is to investigate the effects of n-hexane extracts from bones and internal organs of Japanese eel, Anguilla japonica (HEE), on cyclooxygenase-2 (COX-2)-dependent prostaglandin D₂(PGD₂) generation in stem cell factor (SCF), IL-10, plus LPS-induced mouse bone marrow-derived mast cells (BMMCs) and on passive cutaneous anaphylaxis (PCA) in mice. HEE suppressed SCF/IL-10/LPS-induced PGD₂ generation, and concomitantly reduced COX-2 protein expression dose-dependently. To understand the mechanistic basis for the inhibition of PGD₂ generation by HEE, we examined the effects of HEE on upstream signaling pathways essential for COX-2 induction. HEE was found to inhibit the translocation of nuclear factor-κB (NF-κB) p65 subunit to the nucleus and its DNA-binding ability through the inhibition of TAK1, IKK and IκB phosphorylation. Furthermore, HEE also attenuated mitogen-activated protein kinase (MAPK)-mediated regulation of DNA binding of activator protein-1 (AP-1). Moreover, oral administration of HEE inhibited anti-dinitrophenyl (DNP) IgE-induced PCA in a dose dependent manner. Taken together, the present study provides new insights into the anti-inflammatory activity of HEE, which could be a promising candidate to be used for an inflammatory therapy.

Topics: Anaphylaxis; Anguilla; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone and Bones; Complex Mixtures; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Hexanes; Interleukin-10; Lipopolysaccharides; Male; MAP Kinase Kinase Kinases; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; NF-kappa B; Prostaglandin D2; Transcription Factor AP-1