Allose gallates suppress expression of pro-inflammatory cytokines through attenuation of NF-kappa B in human mast cells

Abstract

Gallotannins are plant-derived, water-soluble polyphenols with wide-ranging biological activities. Mast cell-mediated allergic inflammation is known to cause many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 with immune regulatory properties. Expression of inflammatory cytokines is mainly regulated by a transcription factor, nuclear factor (NF)-kappa B. In the present study, the effect of eight gallotannins on the level of pro-inflammatory cytokines and NF-kappa B activation was investigated in human mast cell line (HMC-1). HMC-1 cells were sensitized by phorbol 12-myristate 13-acetate (PMA) and calcium ionophore (A23187). Among the eight gallotannins from Euphorbia species, three gallotannins such as 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, 1,2,6-tri-O-galloyl-beta-D-allopya nose, and 1,2,3,6-tetra-O-galloyl-beta-D-allopyranose suppressed the gene expression and secretion of pro-inflammatory cytokines in a dose-dependent manner. In addition, these three gallotannins blocked the activation of NF-kappa B as indicated by an NF-kappa B-dependent gene reporter assay. We conclude that these gallotannins may have potential for the treatment of inflammatory diseases through the down-regulation of NF-kappa B-mediated activation of mast cells.