Albaconol, a Plant-Derived Small Molecule, Inhibits Macrophage Function by Suppressing NF-κB Activation and Enhancing SOCS1 Expression

Abstract

Discovery and functional identification of plant-derived small compounds as the immunosuppressant attract much attention these years. Albaconol is a new kind of small compound, prenylated resorcinol, isolated from the fruiting bodies of the inedible mushroom Albatrellus confluens. Our previous studies showed that albaconol can inhibit tumor cell growth and dendritic cell maturation. However, the immunomodulatory roles and the underlying mechanisms of albaconol have not been fully understood. In this study we investigated the effects of albaconol on the proliferation and LPS-induced proinflammatory cytokine production of macrophages. Albaconol, when used at a dose higher than 1.0 µg/ml, inhibited proliferation of RAW264.7 cells in a dose- and time-dependent manner, and could induce cellular apoptosis when used at high dosage (≥ 7.5 µg/ml). Furthermore, we found that albaconol used at a lower dosage without apoptosis induction could significantly inhibit LPS-induced TNF-α, IL-6, IL-1β and NO production in RAW264.7 cells. The inhibition of NF-κB activation and enhancement of SOCS1 expression in LPS-stimulated macrophages by albaconol may contribute to the above immunosuppressive or anti-inflammatory activities of albaconol. Our results suggest that albaconol may be a potential immunosuppressive and anti-inflammatory drug.

Glossary

DMSO

dimethyl sulfoxide

IL-1β

interleukin 1β

IL-6

interleukin 6

IκB

inhibitior of κB

LPS

lipopolysaccharide

NF-κB

nuclear factor-κB

SOCS1

suppressor of cytokine signalling-1

NO

nitric oxide

TNF-α

tumor necrosis factor α