Antibacterial agent triclosan suppresses RBL-2H3 mast cell function.
Triclosan is a broad-spectrum antibacterial agent, which has been shown previously to alleviate human allergic skin disease. The purpose of this study was to investigate the hypothesis that the mechanism of this action of triclosan is, in part, due to effects on mast cell function. Mast cells play important roles in allergy, asthma, parasite defense, and carcinogenesis. In response to various stimuli, mast cells degranulate, releasing allergic mediators such as histamine. In order to investigate the potential anti-inflammatory effect of triclosan on mast cells, we monitored the level of degranulation in a mast cell model, rat basophilic leukemia cells, clone 2H3. Having functional homology to human mast cells, as well as a very well defined signaling pathway leading to degranulation, this cell line has been widely used to gain insight into mast-cell driven allergic disorders in humans. Using a fluorescent microplate assay, we determined that triclosan strongly dampened the release of granules from activated rat mast cells starting at 2 μM treatment, with dose-responsive suppression through 30 μM. These concentrations were found to be non-cytotoxic. The inhibition was found to persist when early signaling events (such as IgE receptor aggregation and tyrosine phosphorylation) were bypassed by using calcium ionophore stimulation, indicating that the target for triclosan in this pathway is likely downstream of the calcium signaling event. Triclosan also strongly suppressed F-actin remodeling and cell membrane ruffling, a physiological process that accompanies degranulation. Our finding that triclosan inhibits mast cell function may explain the clinical data mentioned above and supports the use of triclosan or a mechanistically similar compound as a topical treatment for allergic skin disease, such as eczema.
Graduate School of Biomedical Sciences, University of Maine, Orono, ME 04469, USA. rachel.palmer@maine.edu
Rachel K
RK
Palmer
Lee M
LM
Hutchinson
Benjamin T
BT
Burpee
Emily J
EJ
Tupper
Jonathan H
JH
Pelletier
Zsolt
Z
Kormendy
Alex R
AR
Hopke
Ethan T
ET
Malay
Brieana L
BL
Evans
Alejandro
A
Velez
Julie A
JA
Gosse
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D061207:Calcium Ionophores / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017455:Receptors, IgE / Q000502:physiology; D014260:Triclosan / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D061207:Calcium Ionophores; D017455:Receptors, IgE; D014260:Triclosan