Biosurfactant mannosyl-erythritol lipid inhibits secretion of inflammatory mediators from RBL-2H3 cells

Background: Biosurfactant mannosyl-erythritol lipids (MELs) are glycolipids produced by microbes that have various biological activities. It has been reported that MELs exhibit excellent surface-activity and also various bioactivities, such as induction of cell differentiation and apoptosis. However, little is known about their action related to drug discovery or drug seeds. Methods: We investigated the effects of MELs on the secretion of inflammatory mediators from mast cells that play a central role in allergic responses. Mast cells secrete three kinds of inflammatory mediators and we quantified these secreted mediators by photometer or ELISA. The action mechanisms of MELs were studied by Ca2+-sensitive fluorescence dye and Western blotting of phosphorylated proteins. Results: MELs inhibited exocytotic release by antigen stimulation in a dose-dependent manner. We also found that MELs inhibited antigen-induced secretion of leukotriene C-4 and cytokine TNF-alpha (tumor necrosis factor-alpha). The inhibitory action of MELs on mediator secretion was mediated by inhibition of Ca2+ increase, phosphorylation of MAP kinases and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) that serve as a molecular machinery for exocytotic membrane fusion. Conclusions: MELs have anti-inflammatory action inhibiting the secretion of inflammatory mediators from mast cells. General significance: MELs affects two of major intracellular signaling pathways including Ca2+ increase and MAP kinases. MELs also inhibited the phosphorylation of SNARE proteins that is crucial for not only exocytosis but also intracellular vesicular trafficking. (C) 2011 Elsevier B.V. All rights reserved.