Journal of Clinical & Experimental Dermatology Research
Open Access
ISSN: 2155-9554
+44 1478 350008
ISSN: 2155-9554
+44 1478 350008
Raphael Coatmeur
Faculty of Pharmacy, France
Scientific Tracks Abstracts: J Clin Exp Dermatol Res
The skin is the body’s first line of defence against aggressions such as pathogens, toxins, and harmful pollutants. The aryl hydrocarbon receptor (AHR) is a transcription factor playing a crucial role in skin protection. Indeed, AHR was initially described as a key chemo-sensor to environmental pollutants, as it regulates xenobiotic metabolism enzymes expression. It also plays an important role in the regulation of several genes involved in inflammation and immune response. However, prolonged activation of AHR by exogenous chemicals, such as Polycyclic Aromatic Hydrocarbons or dioxins, can lead to its deregulation and potentially to the development of skin diseases (atopic dermatitis, psoriasis, and skin cancers).The aim of this project is to modulate AHR activity in the skin to develop innovative treatments using our non-competitive antagonist, MM107, synthesized by the PROTAC technique. In primary human keratinocytes, after AHR stimulation by an agonist, Benzo[a]Pyren (BAP), we observed by qRt-PCR that MM107 inhibited the induction of AHR target genes expression involved in inflammation. Inversely, the expression of the anti inflammatory cytokine TGFβ was not affected by BAP, whereas MM107 increased it. These results were confirmed, at the protein level, for AHR itself and NF-κB. In addition, the catalytic activities of CYP1A1&1B1 and MMP1&13 were significantly decreased. MM107, in presence of an AHR agonist, also decreased the production of the pro-inflammatory cytokines TNF-α, IL-1β and IL-8, while increasing the anti-inflammatory cytokine TGF-β level. Our data confirmed that MM107, our proprietary molecule designed to specifically target AHR, could improve treatments of inflammatory skin diseases in which AHR has been involved. In addition, the modulation of AHR activity goes beyond the therapeutic field and reaches the cosmetic field in their quest for new anti-pollutant products.
Raphael Coatmeur has obtained with honours two research Masters in Pharmacokinetics and Cosmetic Formulation. He is currently completing his PhD at the Mediterranean Institute of Marine and Continental Biology at the Faculty of Pharmacy in Marseille in partnership with the biotech company Alphenyx (CIPHRE grant) and should defend his PhD in June 2022.