Morin inhibits Fyn kinase in mast cells and IgE-mediated type I hypersensitivity response in vivo.
Mast cells are responsible for IgE-mediated allergic responses. Although dietary flavonoid morin has been known to suppress mast cell activation, its in vivo anti-allergic activity and the underlying mechanisms remain are largely unknown. In this study, we determine whether morin suppresses IgE-mediated allergic responses in an animal model and its mechanism of action. Morin suppressed IgE-mediated PCA in mice (ED50 23.9 mg/kg) and inhibited degranulation and production of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-4 in antigen (Ag)-stimulated mast cells. The mechanism of action was a follows. Morin inhibited the activating phosphorylation of spleen tyrosine kinase (Syk) and linker for activation of T cells (LAT) in rat basophilic leukemia (RBL)-2H3 cells and bone marrow-derived mast cells (BMMCs). Akt and the mitogen-activated protein (MAP) kinases, p38, extracellular signal-regulated kinase (ERK)1/2, and c-Jun N-terminal kinase (JNK) were inhibited as well. In vitro kinase assay indicated that Fyn kinase, not Lyn and Syk, was inhibited by morin in a dose-dependent manner (IC50 5.7 microM). In conclusion, the results suggest that morin suppresses the IgE-mediated allergic response by primarily inhibiting Fyn kinase in mast cells.
Department of Immunology and Physiology, College of Medicine, Konkuk University, 322 Danwol-dong, Chungju, Republic of Korea.
Jie Wan
JW
Kim
Jun Ho
JH
Lee
Bang Yeon
BY
Hwang
Se Hwan
SH
Mun
Na Young
NY
Ko
Do Kyun
DK
Kim
Bokyung
B
Kim
Hyung Sik
HS
Kim
Young Mi
YM
Kim
Wahn Soo
WS
Choi
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006969:Hypersensitivity, Immediate / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases; D051381:Rats; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*; D047309:Flavones
D005419:Flavonoids; D007073:Immunoglobulin E; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases; C008548:morin; D047309:Flavones; C490512:Frk protein, mouse