Inhibitory effect and action mechanism of diphlorethohydroxycarmalol (DPHC) on the production of interleukin-6 in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells

Abstract

Inflammatory response is regulated and mediated by various immune cells, such as onocyte and macrophage, and especially macrophages are important players that are closely related to the initiation, propagation, and resolution of inflammation. Interleukin-6 (L-6) is a representative pro-inflammatory cytokine generated in stimulated macrophages and may cause deleterious inflammatory states. Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from Ishigeokamuarae, a brown algae. This study was conducted to investigate the anti-inflammatory effect and action mechanism of DPHC in the lipopolysaccharide (LPS) stimulated RAW 264.7 murine macrophages. The experimental results showed that DPHC inhibited LPS-induced IL-6 production in a dose dependent manner at concentration of 12.5, 25, 50, and 100 μM. DPHC also suppressed the phosphorylation and the nuclear translocation of NF-κB (p65 and p50 subunits), a central signaling molecule in LPS induced inflammation process. Furthermore, the known inhibitors of NF-κB (pyrrolidinedithiocarbamate; PDTC, N-tosyl-L-phenylalaninechloromethyl ketone; TPCK, parthenolide) strongly inhibited IL-6 production in this system. However, DPHC had no or only minimal effects on the mitogen activated protein kinase pathways (JNK, ERK and P-38) and STAT1, 3, and 5 pathways activated by LPS. In conclusion, the present study demonstrates that DPHC could inhibit IL-6 production through the suppression of NF-κB activation and is suggested as a potential candidate for treating inflammatory diseases.