interleukin-8 and acanthoic-acid

Acanthoic acid, a pimaradiene diterpene isolated from Acanthopanax koreanum, has been reported to have anti-inflammatory activities. However, the effect of acanthoic acid on vascular inflammation has not been investigated. The aim of this study was to investigate the anti-inflammatory effects of acanthoic acid on lipopolysaccharide (LPS)-induced inflammatory response in human umbilical vein endothelial cells (HUVECs). The production of cytokines TNF-α and IL-8 was detected by ELISA. The expression of VCAM-1, ICAM-1, E-selectin, NF-κB and LXRα were detected by Western blotting. Adhesion of monocytes to HUVECs was detected by monocytic cell adhesion assay. The results showed that acanthoic acid dose-dependently inhibited LPS-induced TNF-α and IL-8 production. Acanthoic acid also inhibited TNF-α-induced IL-8 and IL-6 production. LPS-induced endothelial cell adhesion molecules, VCAM-1 and ICAM-1 were also inhibited by acanthoic acid. Acanthoic acid inhibited LPS-induced NF-κB activation. Furthermore, acanthoic acid dose-dependently up-regulated the expression of LXRα. In addition, our results showed that the anti-inflammatory effect of acanthoic acid was attenuated by transfection with LXRα siRNA. In conclusion, the anti-inflammatory effect of acanthoic acid is due to its ability to activate LXRα. Acanthoic acid may be a therapeutic agent for inflammatory cardiovascular disease.

Topics: Anti-Inflammatory Agents; Cell Adhesion; Cell Survival; Diterpenes; E-Selectin; Human Umbilical Vein Endothelial Cells; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Lipopolysaccharides; Liver X Receptors; NF-kappa B; Orphan Nuclear Receptors; RNA, Small Interfering; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Intestinal epithelial cells (IECs) can produce cytokines and chemokines that play an important role in the mucosal immune response. Regulation of this production is important to prevent inflammatory tissue damage. The root and stem barks of Acanthopanax species have been used as a tonic and sedative as well as in the treatment of rheumatism and diabetes. The aim of this study was to examine the inhibitory effect of acanthoic acid isolated from Acanthopanax koreanum (Araliaceae), on IL-8 production via mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappaB) in TNF-alpha-stimulated human colon epithelial cells.. HT29 cells were stimulated with TNF-alpha in the presence or absence of acanthoic acid. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-PCR (RT-PCR). MAPK activation and IkappaB/NF-kappaB expression were assessed by Western blot analysis. NF-kappaB activation was determined using immunofluorescence localization and electrophoretic mobility shift assay (EMSA).. Acanthoic acid suppressed TNF-alpha-induced IL-8 production in a dose-dependent manner. Furthermore, acanthoic acid inhibited TNF-alpha-induced MAPKs (p38, JNK1/2, and ERK1/2) activation, IkappaB degradation, NF-kappaB nuclear translocation, and NF-kappaB/DNA binding activity.. Acanthoic acid might inhibit TNF-alpha-mediated IL-8 production by blocking in both the MAPKs and NF-kappaB pathways in HT29 cells.

Topics: Cell Line; Diterpenes; Dose-Response Relationship, Drug; Eleutherococcus; Enzyme-Linked Immunosorbent Assay; Humans; I-kappa B Kinase; Interleukin-8; Intestinal Mucosa; Mitogen-Activated Protein Kinases; NF-kappa B; Plant Bark; Plant Extracts; Protein Binding; Protein Serine-Threonine Kinases; Protein Transport; RNA, Messenger; Transcription Factor AP-1; Tumor Necrosis Factor-alpha