Inhibitory effect of porphyran on lipopolysaccharide-induced activation of human immune cells.

• Pyropia yezoensis porphyran inhibits LPS-induced proinflammatory cytokines in human PBMCs. • Porphyran suppresses LPS-induced human MODC and PBDC activation. • LPS binding to TLR4/MD2 complex is interrupted by porphyran in human PBDCs. In mice, porphyran extracted from Pyropia yezoensis exerts anti-inflammatory effects and suppresses lipopolysaccharide (LPS)-induced immune activation and sepsis. Here, we investigated inhibition of LPS-induced activation of human immune cells by porphyran and the underlying mechanisms. We demonstrated that porphyran may inhibit LPS-induced proinflammatory cytokine production in peripheral blood mononuclear cells, monocyte-derived dendritic cells, and peripheral blood dendritic cells. We also observed that porphyran-mediated LPS-induced activation of DC suppressed syngeneic T cell proliferation, resulting in reduced production of interferon-γ. The mechanism of LPS-induced immune cell activation requires the activation of toll like receptor 4 following binding of LPS to myeloid differentiation factor 2 (MD2). Additionally, we show that porphyran competes with LPS for binding to MD2 and thereby suppresses immune cell activation. Porphyran may, therefore, be a promising therapeutic candidate for the treatment of endotoxin-mediated septic shock and inflammation in humans. [ABSTRACT FROM AUTHOR]