Cytokines and signal transduction pathways mediated by anthralin in alopecia areata-affected Dundee experimental balding rats.
Although many therapeutic modalities have been tested on alopecia areata, patient outcomes have been disappointing. Use of animal models would help to develop more efficient therapies as well as understanding therapeutic mechanisms. We have demonstrated that 0.1% topical anthralin ointment is 100% effective in restoring follicular activity in Dundee experimental balding rats. This is the most promising topical treatment for Dundee experimental balding rats among the therapeutic agents tested on this model. Various cytokines have been shown to be associated with the pathogenesis of alopecia areata. To test whether any of these cytokines might be modulated by anthralin, an RNase protection assay and the real-time polymerase chain reaction were performed to compare their expression between anthralin-treated and control skins. These experiments showed that expression of tumor necrosis factor-alpha and interferon-gamma was inhibited by anthralin, whereas expression of interleukin-1alpha/beta and their receptor antagonist, interleukin-1Ra, and interleukin-10 was stimulated by anthralin. In addition, using an antibody-based multi-immunoblotting technique, we found that certain signaling regulatory proteins were modulated by anthralin. Their potential roles in reversing the autoimmune-arrested follicular activity in Dundee experimental balding rats are discussed.
Tang
Liren
L
Division of Dermatology, Department of Medicine, University of British Columbia, Vancouver Hospital, Canada. ltang@vanhosp.bc.ca
Cao
Liping
L
Pelech
Steven
S
Lui
Harvey
H
Shapiro
Jerry
J
D000506:Alopecia Areata / Q000503:physiopathology*; D000818:Animals; D000875:Anthralin / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D018859:Hair Follicle / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011922:Rats, Mutant Strains; D015398:Signal Transduction / Q000187:drug effects*
D016207:Cytokines; D000875:Anthralin