Saturday, November 26, 2016

Carbon-derived environmental pollutants induce atopic dermatitis-associated skin itch via Artemin

It has been recognized that various organic [carbon-derived] pollutants activate the transcription factor AhR (aryl hydrocarbon receptor). AhR initiate the expression of genes encoding detoxification enzymes in response to xenobiotics (foreign chemicals, not ordinarily found in the body). Such response, if overwhelmed, could lead to pathology. As an example, studies have revealed a relationship between air pollution and the prevalence and exacerbation of atopic dermatitis (AD), a chronic, itchy skin inflammation. 

Initially the authors created mice that would constitutively express Ahr in skin epithelial cells (AhR-CA mice). These mice developed more itchy skin and their skin contained more of inflammatory cytokines and cells.

In addition, skin of Ahr-CA mice contained more abundant network of neurons associated with itching behavior (TRPV1+ neurons).

The authors found that neurothropic factor Artemin was highly expressed in skin of Ahr-CA mice.

Depletion of Artemin via antibody injection reduced itching behavior and skin epithelial neuronal density.

Finally, mice lacking Ahr in skin epithelial cells (approximately 70% efficiency for the deletion of Ahr specifically in the epidermis) expressed reduced level of Artemin and display less skin inflammation in response to organic pollutants (though skin-specific Artemin deficiency would have been more valuable here).

In summary, this study suggests that air pollution by carbon derivatives, such as diesel exhaust particles, could initiate manifestation of atopic dermatitis by hyper-activation of the skin Ahr function.

David Usharauli

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