title: Spiraeoside inhibits mast cells activation and IgE-mediated allergic responses by suppressing phospholipase C-γ-mediated signaling.
abstract: Mast cells are responsible for IgE-mediated allergic responses through the secretion of various inflammatory cytokines and mediators. Therefore, the pharmacological regulation of mast cell activation is an important goal in the development of novel anti-allergic drugs. In this study, we found that spiraeoside (SP) inhibits mast cell activation and allergic responses in vivo. SP dose-dependently inhibited the degranulation induced by IgE-antigen (Ag) stimulation in RBL-2H3 mast cells without cytotoxic effects. At the molecular level, SP reduced the Ag-induced phosphorylation and subsequent activation of phospholipase C-γ2 (PLC-γ2). Moreover, SP inhibited the phosphorylation of spleen tyrosine kinase (Syk), linker for activation of T cells (LAT), and downstream MAPKs, such as ERK1/2, p38, and JNK, eventually attenuating expression of TNF-α and IL-4. Finally, we found that SP significantly inhibited IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Taken together, our results strongly suggest that SP suppresses IgE-mediated mast cell activation and allergic responses by inhibiting Lyn-induced PLC-γ2/MAPK signaling in mast cells.
authors.affiliation: School of Nano-Biotechnology & Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea., Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Jung Kuk
authors.initials: JK
authors.lastname: Kim
authors.forename: Young-Kyo
authors.initials: YK
authors.lastname: Seo
authors.forename: Sehoon
authors.initials: S
authors.lastname: Park
authors.forename: Soo-Ah
authors.initials: SA
authors.lastname: Park
authors.forename: Seyoung
authors.initials: S
authors.lastname: Lim
authors.forename: Susie
authors.initials: S
authors.lastname: Lee
authors.forename: Ohman
authors.initials: O
authors.lastname: Kwon
authors.forename: Jeong Kon
authors.initials: JK
authors.lastname: Seo
authors.forename: Ung-Kyu
authors.initials: UK
authors.lastname: Choi
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
mesh_terms: D000818:Animals; D002460:Cell Line / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects* / Q000276:immunology; D051966:Phospholipase C gamma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D007073:Immunoglobulin E; D011794:Quercetin; D019061:src-Family Kinases; D051966:Phospholipase C gamma; C080613:spiraeoside
keywords: Lyn/Syk kinase; MAPK; PLC-γ; Spiraeoside; allergic response; degranulation; dégranulation; mast cells; mastocytes; réponse allergique; spiraeoside