Anti-inflammatory activity of fisetin in human mast cells (HMC-1).
Mast cells play an important role in the pathogenesis of allergic diseases through the release of inflammatory mediators such as histamine, cysteinyl leukotrienes, cytokines, and chemokines. Flavonoids, like fisetin are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. The aim of our study was to examine whether fisetin modulates inflammatory reaction in stimulated human mast cells (HMC-1). Fisetin decreased phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated gene expression and production of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-4, IL-6, and IL-8 in HMC-1 cells. Fisetin inhibited PMACI-induced phosphorylation of p38 mitogen-activated protein kinase, extracellular-regulated kinase, and c-Jun N-terminal kinase. In addition, fisetin suppressed nuclear factor (NF)-kappaB activation induced by PMACI, leading to expression of IkappaB-alpha phosphorylation and degradation. Fisetin suppressed powerful induction of NF-kappaB promoter-mediated luciferase activity. These pharmacological actions of fisetin produce new suggestion that fisetin is a potential medicine for treatment of inflammatory diseases through the down-regulation of mast cell activation.
Park
Hyo-Hyun
HH
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, South Korea.
Lee
Soyoung
S
Oh
Jae-Min
JM
Lee
Myeung-Su
MS
Yoon
Kwon-Ha
KH
Park
Byoung Hyun
BH
Kim
Jeong Woo
JW
Song
Haheon
H
Kim
Sang-Hyun
SH
D000893:Anti-Inflammatory Agents; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005419:Flavonoids; D044948:Flavonols; D016328:NF-kappa B; D008156:Luciferases; D048049:Extracellular Signal-Regulated MAP Kinases; C017875:fisetin