Effects of Resveratrol on Mast Cell Degranulation and Tyrosine Phosphorylation of the Signaling Components of the IgE Receptor

Abstract

The molecular mechanism of how resveratrol inhibits mast cell degranulation was studied by examining its effects on the signaling components of the high affinity IgE receptor (FcεRI) pathway. Resveratrol inhibited mast cell degranulation in a dose-dependent manner and reduced the FcεRI-mediated tyrosine phosphorylation of ERK and PLCγ1 but not of Syk and PLCγ2. U-73 122 and PD98059, which are PLC and MEK inhibitors, also had inhibitory effects on mast cell degranulation. These results suggest that FcεRI-mediated tyrosine phosphorylation of PLCγ1 and ERK could be potential cellular targets of resveratrol for the inhibition of mast cell degranulation.

Abbreviations

FcεRI:high affinity IgE receptor

ERK:extracellular signal regulated kinase

MEK:mitogen-activated protein kinase kinase

MAPK:mitogen-activated protein kinase

PLCγ:phospholipase C-γ

References

• 1 Jang M, Cai L, Udeani G O, Slowing K V, Thomas C F, Beecher C W. et al . Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.  Science. 1997;  275 218-20
• 2 Kimura Y, Okuda H, Arichi S. Effects of stilbenes on arachidonate metabolism in leukocytes.  Biochim Biophys Acta. 1985;  834 275-8
• 3 Kawada N, Seki S, Inoue M, Kuroki T. Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells.  Hepatology. 1998;  27 1265-74
• 4 Stewart J R, Ward N E, Ioannides C G, O’Brian C A. Resveratrol preferentially inhibits protein kinase C-catalyzed phosphorylation of a cofactor-independent, arginine-rich protein substrate by a novel mechanism.  Biochemistry. 1999;  38 13 244-51
• 5 Cheong H, Ryu S Y, Kim K M. Anti-allergic action of resveratrol and related hydroxystilbenes.  Planta Med. 1999;  65 266-8
• 6 Baolin L, Inami Y, Tanaka H, Inagaki N, Iinuma M, Nagai H. Resveratrol inhibits the release of mediators from bone marrow-derived mouse mast cells in vitro .  Planta Med. 2004;  70 305-9
• 7 Quilez A M, Saenz M T, Garcia M D, de la Puerta R. Phytochemical analysis and anti-allergic study of Agave intermixta Trel. and Cissus sicyoides L.  J Pharm Pharmacol. 2004;  56 1185-9
• 8 Schwartz L B, Austen K F, Wasserman S I. Immunologic release of beta-hexosaminidase and beta-glucuronidase from purified rat serosal mast cells.  J Immunol. 1979;  123 1445-50
• 9 Martin U, Roemer D. Ketotifen: a histamine release inhibitor.  Monogr Allergy. 1977;  12 145-9
• 10 Fischer B, Schmutzler W. Inhibition by azelastine of the immunologically induced histamine release from isolated guinea pig mast cells.  Arzneimittelforschung. 1981;  31 1193-5
• 11 Choi H S, Kim K M. Tanshinones inhibit mast cell degranulation by interfering with IgE receptor-mediated tyrosine phosphorylation of PLCgamma2 and MAPK.  Planta Med. 2004;  70 178-80
• 12 Eiseman E, Bolen J B. Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases.  Nature. 1992;  355 78-80
• 13 Parravicini V, Gadina M, Kovarova M, Odom S, Gonzalez-Espinosa C, Furumoto Y. et al . Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation.  Nat Immunol. 2002;  3 741-8
• 14 Benhamou M, Ryba N J, Kihara H, Nishikata H, Siraganian R P. Protein-tyrosine kinase p72syk in high affinity IgE receptor signaling. Identification as a component of pp72 and association with the receptor gamma chain after receptor aggregation.  J Biol Chem. 1993;  268 23 318-24
• 15 Barker S A, Caldwell K K, Pfeiffer J R, Wilson B S. Wortmannin-sensitive phosphorylation, translocation, and activation of PLCgamma1, but not PLCgamma2, in antigen-stimulated RBL-2H3 mast cells.  Mol Biol Cell. 1998;  9 483-96
• 16 Offermanns S, Jones S V, Bombien E, Schultz G. Stimulation of mitogen-activated protein kinase activity by different secretory stimuli in rat basophilic leukemia cells.  J Immunol. 1994;  152 250-61
• 17 Yoon E, Beom S, Cheong H, Kim S, Oak M, Cho D. et al . Differential regulation of phospholipase C gamma subtypes through Fc epsilon RI, high affinity IgE receptor.  Biochem Biophys Res Commun. 2004;  325 117-23
• 18 Naveen B, Shankar B S, Subrahmanyam G. FcepsilonRI cross-linking activates a type II phosphatidylinositol 4-kinase in RBL 2H3 cells.  Mol Immunol. 2005;  42 1541-9
• 19 Oak M H, Cheong H, Kim K M. Activation of Fc epsilon RI inhibits the pyruvate kinase through direct interaction with the gamma-chain.  Int Arch Allergy Immunol. 1999;  119 95-100