Ancient medicine

Ellen

The working mechanism of an ancient dermatological therapy revealed

In a recent publication in The Journal of Clinical Investigation, Ellen van den Bogaard and Joost Schalkwijk (Dept of Dermatology), together with collaborators from Nijmegen and Germany, demonstrate the molecular mechanism of the oldest known dermatological therapy. Topical application of coal tar cream is known to be a highly efficacious and safe treatment for inflammatory skin diseases such as atopic dermatitis. However, this therapy is progressively abandoned by dermatologists due to cosmetical aspects and suspected (but unsubstantiated) safety concerns. This and the unknown molecular working mechanism has precluded investigation of coal tar by big pharma.

In the current study, it was shown that skin barrier defects in atopic dermatitis patients are restored  by coal tar. Epidermal cells, the keratinocytes, produce proteins which are essential for a proper barrier function of the skin. This barrier is compromised in patients due to a genetic predisposition (mutation of thefilaggringene); in addition, the Th2-cytokine mediated inflammation further downregulates the expression of skin barrier proteins. Th2 cytokines are known to activate the IL-4/STAT6 signaling cascade. In keratinocytes this leads to production of chemokines and also to  downregulation of epidermal differentiation. Coal tar was shown to act on this pathway by causing dephosphorylation of STAT6, resulting in normalization of chemokine levels and expression of skin barrier proteins. Activation of the arylhydrocarbon receptor (AhR) was proven to be crucial in the effects mediated by coal tar. Thus, the therapeutic effect of coal tar is bipartite: the improved skin barrier descreases exposure to potential exogens/allergens that trigger inflammation, and the existing inflammation is dampened by suppression of chemokine production and diminished STAT6 signaling. These two mechanisms breach the vicious circle of inflammation, thereby enabling recovery of normal skin function.

These findings will open a new avenue for the development of mechanism-based drugs for chronic inflammatory skin diseases such as atopic dermatitis and will rehabilitate the use of coal tar in dermatological practice.

Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis.
van den Bogaard EH, Bergboer JG, Vonk-Bergers M, van Vlijmen-Willems IM, Hato SV, van der Valk PG, Schröder JM, Joosten I, Zeeuwen PL, Schalkwijk J.
J Clin Invest. 2013 Jan 25. doi: 10.1172/JCI65642. [Epub ahead of print]

 

 


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