| RRC ID |
6021
|
| 著者 |
Miyata N, Gon Y, Nunomura S, Endo D, Yamashita K, Matsumoto K, Hashimoto S, Ra C.
|
| タイトル |
Inhibitory effects of parthenolide on antigen-induced microtubule formation and degranulation in mast cells.
|
| ジャーナル |
Int Immunopharmacol
|
| Abstract |
Pharmacological modulation of IgE-mediated mast cell activation is important to the development of anti-allergic reagents. In this study, we investigated the effects of parthenolide (PTL) on high-affinity IgE receptor (FcepsilonRI)-induced degranulation in mast cells. PTL dose-dependently inhibited degranulation induced by IgE.antigen stimulation in RBL-2H3 cells and BMMCs. Although PTL is a potent NF-kappaB inhibitor by targeting IkappaB kinase complex, NF-kappaB inhibition by other IkappaB kinase inhibitors did not inhibit degranulation in mast cells. IgE.antigen-induced microtubule formation is well known to be critical for degranulation in mast cells. Immunocytochemical study with anti-alpha-tubulin antibody revealed that PTL significantly inhibited IgE.antigen-induced microtubule formation. However, PTL, as well as nocodazol, had no significant effects on degranulation in the fyn-deficient BMMCs, suggesting that inhibitory effects of PTL in the microtubule formation are fyn dependent. We further demonstrated that in vivo administration of PTL in mice strongly inhibited passive cutaneous anaphylaxis reaction. The present study provides a possibility to develop potent reagents against mast cell activation based on an inhibition of microtubule formation.
|
| 巻・号 |
8(6)
|
| ページ |
874-80
|
| 公開日 |
2008-6-1
|
| DOI |
10.1016/j.intimp.2008.02.002
|
| PII |
S1567-5769(08)00055-6
|
| PMID |
18442792
|
| MeSH |
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Cell Degranulation*
Cell Line
Cells, Cultured
I-kappa B Kinase / antagonists & inhibitors
I-kappa B Kinase / metabolism
Immunoglobulin E / immunology*
Mast Cells / drug effects
Mast Cells / immunology*
Mast Cells / metabolism
Mast Cells / ultrastructure
Mice
Mice, Inbred C57BL
Microtubules / drug effects
Microtubules / metabolism*
NF-kappa B / antagonists & inhibitors
NF-kappa B / metabolism
Nocodazole / pharmacology
Passive Cutaneous Anaphylaxis / drug effects
Passive Cutaneous Anaphylaxis / immunology
Receptors, IgE / immunology*
Sesquiterpenes / pharmacology*
Tubulin Modulators / pharmacology
|
| IF |
3.943
|
| 引用数 |
24
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
IMMUNOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC01000 |
