Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 8, Issue 6, Pages 874-880Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2008.02.002
Keywords
parthenolide; mast cell; allergy; microtubule; fyn
Categories
Ask authors/readers for more resources
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 (Fc epsilon RI)-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-kappa B inhibitor by targeting I kappa B kinase complex, NF-kappa B inhibition by other I kappa B 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. (C) 2008 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available