RSS-Feed abonnieren
DOI: 10.1055/s-2004-815498
Tanshinones Inhibit Mast Cell Degranulation by Interfering with IgE Receptor-Mediated Tyrosine Phosphorylation of PLCγ2 and MAPK
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (02-PJ2-PG3-21 203-0001)Publikationsverlauf
Received: July 7, 2003
Accepted: October 3, 2003
Publikationsdatum:
02. März 2004 (online)
Abstract
Recently we have isolated four active components from Tanshen (the root of Salvia miltiorrhiza Bunge, Labiatae) responsible for the anti-allergic activities. In this study, the molecular mechanism of action of tanshinones for the inhibition of mast cell degranulation was investigated by testing their effects on the signaling components of the high affinity IgE receptor FcεRI. Activation of FcεRI produced immediate tyrosine phosphorylation of Syk, mitogen-activated protein kinase extracellular signal-regulated kinase, ERK1/ERK2 (p44, p42), and phospholipase Cγ2 (PLCγ2). 5,16-Dihydrotanshinone-I possessed the strongest inhibitory effects on mast cell degranulation and markedly reduced FcεRI-mediated tyrosine phosphorylation of ERK and PLCγ2. This suggests that tanshinones possibly exert their anti-allergic activities by affecting FcεRI-mediated tyrosine phosphorylation of ERK and PLCγ2.
Abbreviations
FcεRI:high affinity IgE receptor
ERK:extracellular signal regulated kinase
PLC: phospholipase C
References
- 1 Kim S Y, Moon T C, Chang H W, Son K H, Kang S S, Kim H P. Effects of tanshinone I isolated from Salvia miltiorrhiza Bunge on arachidonic acid metabolism and in vivo inflammatory responses. Phytother Res. 2002; 16 616-20
- 2 Kang B Y, Chung S W, Kim S H, Ryu S Y, Kim T S. Inhibition of interleukin-12 and interferon-gamma production in immune cells by tanshinones from Salvia miltiorrhiza . Immunopharmacology. 2000; 49 355-61
- 3 Ryu S Y, Oak M H, Kim K M. Inhibition of mast cell degranulation by tanshinones from the roots of Salvia miltiorrhiza . Planta Med. 1999; 65 654-5
- 4 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
- 5 Cheong H, Ryu S Y, Kim K M. Anti-allergic action of resveratrol and related hydroxystilbenes. Planta Med. 1999; 65 266-8
- 6 Fischer B, Schmutzler W. Inhibition by azelastine of the immunologically induced histamine release from isolated guinea pig mast cells. Arzneimittelforschung. 1981; 31 1193-5
- 7 Ryu S Y, Lee C O, Choi S U. In vitro cytotoxicity of tanshinones from Salvia miltiorrhiza . Planta Med. 1997; 63 339-42
- 8 Eiseman E, Bolen J B. Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases. Nature. 1992; 355 78-80
- 9 Parravicini V, Gadina M, Kovarova M, Odom S, Gonzalez-Espinosa C, Furumoto Y, Saitoh S, Samelson L E, O'Shea J J, Rivera J. Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nat Immunol. 2002; 3 741-8
- 10 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
- 11 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
- 12 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
Kyeong-Man Kim, Ph. D.
Pharmacology Laboratory
College of Pharmacy
Chonnam National University
Kwang-Ju, 500-757
Korea
Fax: +82-62-530-2949
eMail: kmkim@chonnam.ac.kr