Resveratrol Inhibits the Release of Mediators from Bone Marrow-Derived Mouse Mast cells in vitro

Abstract

Resveratrol is a natural phytoalexin occurring in grapes, vines and peanuts and possesses both antitumor and antioxidation capabilities. Its chemoprotective actions are attributed partially to its anti-inflammation effect. The present study is aimed at checking the inhibitory actions of resveratrol on the release of mediators from bone marrow-derived mouse mast cells (BMMC) in vitro. Mast cells were prepared by isolating bone marrow cells from intact mice femora and culturing them for 4 weeks in the presence of IL-3 and FCS. The release reaction was triggered by IgE or calcium ionophore (A23187). Mediated by IgE, the release of histamine and tumor necrosis factor-α was significantly inhibited by resveratrol at a concentration of 100 μM; IgE-mediated release of leukotrienes and prostaglandin D₂ was also strongly suppressed at concentrations of 100 and 10 μM. Also, A23187-mediated release of histamine and leukotrienes release was strongly reduced by resveratrol at concentrations of 100 and 10 μM, respectively. Resveratrol exhibited its behavior without a significant cytotoxic activity against mast cells. In conclusion, resveratrol is a potent non-selective inhibitor of mediator release from activated mast cells and deserves further investigation of its biological modulations.

Key words

Resveratrol - bone marrow-derived mouse mast cells - histamine - leukotrienes - prostaglandin D₂ - tumor necrosis factor-α - cytotoxicity

References

• 1 Kimura Y, Okuda H. Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice.  J Nutr. 2001;  131 1844-9
• 2 Leonard S S, Xia C, Jiang B H, Stinefelt B, Klandorf H, Harris G K. et al . Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses.  Biochem Biophys Res Commun. 2003;  309 1017-26
• 3 Jang M, Cai L, Geogo O, Udeani K, Slowing V. et al . Cancer chemopreventive activity of resveratrol, a nature product derived from grapes.  Science. 1997;  275 218-20
• 4 Huang K S, Lin M, Cheng G F. Anti-inflammatory tetramers of resveratrol from the roots of Vitis amurensis and conformations of the seven-membered ring in some oligostilbenes.  Phytochemistry. 2001;  58 357-62
• 5 Kulanthavivel P, Janzen W P, Ballas L M, Jiang J B, Hu C Q, Darges J W. Naturally occurring protein kinase C inhibitors; II. Isolation of oligomeric stilbenes from Caragana sinica .  Planta Med. 1995;  61 41-4
• 6 Bertelli A A, Ferrara F, Diana G, Fulgenzi A, Corsi M, Ponti W. et al . Resveratrol, a natural stilbene in grapes and wine, enhances intraphagocytosis in human promonocytes: a co-factor in anti-inflammatory and anticancer chemopreventive activity.  Int J Tissue React. 1999;  21 93-104
• 7 Sakurai T, Inakaki N, Nagai H. The effect of anti-tumor necrosis factor (TNF-α) monoclonal antibody to allergic cutaneous late phase reaction in mice.  Life Sci. 1994;  54 291-5
• 8 Sanchez de Rojas V R, Somoza B, Ortega T, Villar A M. Isolation of vasodilatory active flavonoids from the traditional remedy Satureja obovata .  Planta Med. 1996;  62 272-4
• 9 Kimata M, Inagaki N, Nagai H. Effects of luteolin and other flavonoids on IgE-mediated allergic reactions.  Planta Med. 2000;  66 25-9
• 10 Tamatodani A, Wada H, Iwada T, Watanabe T. High-performance liquid chromatographic determination of plasma and brain histamine without previous purification of biological samples: Cation-exchange chromatography coupled with post-column derivatization fluorometry.  J Chromatogr. 1985;  334 115-23
• 11 Ogasawara T, Muraami M, Suzuki-Nishimura T, Uchida M K, Kudo I. Mouse bone marrow-derived mast cells undergo exocytosis prostanoid generation, and cytokine expression in response to G-protein-activating polybasic compounds after coculture with fibroblasts in the presence of c-kit ligand.  J Immunol. 1997;  158 393-404
• 12 Martinez J, Moreno J J. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production.  Biochemical Pharmacology. 2000;  59 865-70
• 13 Gao X, Xu Y, Janakiraman N, Chapman R A, Gautam S C. Immunomodulatory activity of resveratrol: Suppression of lymphocyte proliferation, development of cell-mediated cytotoxity, and cytokine production.  Biochemical Pharmacology. 2001;  62 1299-308
• 14 Kimura Y, Okuda H, Kubo M. Effects of stilbenes, isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes.  J Ethnopharmacol. 1995;  45 131-9