A Tissue-Engineered Human Psoriatic Skin Model to Investigate the Implication of cAMP in Psoriasis: Differential Impacts of Cholera Toxin and Isoproterenol on cAMP Levels of the Epidermis.
Pathological and healthy skin models were reconstructed using similar culture conditions according to well-known tissue engineering protocols. For both models, cyclic nucleotide enhancers were used as additives to promote keratinocytes' proliferation. Cholera toxin (CT) and isoproterenol (ISO), a beta-adrenergic agonist, are the most common cAMP stimulators recommended for cell culture. The aim of this study was to evaluate the impact of either CT or ISO on the pathological characteristics of the dermatosis while producing a psoriatic skin model. Healthy and psoriatic skin substitutes were produced according to the self-assembly method of tissue engineering, using culture media supplemented with either CT (10-10 M) or ISO (10-6 M). Psoriatic substitutes produced with CT exhibited a more pronounced psoriatic phenotype than those produced with ISO. Indeed, the psoriatic substitutes produced with CT had the thickest epidermis, as well as contained the most proliferating cells and the most altered expression of involucrin, filaggrin, and keratin 10. Of the four conditions under study, psoriatic substitutes produced with CT had the highest levels of cAMP and enhanced expression of adenylate cyclase 9. Taken together, these results suggest that high levels of cAMP are linked to a stronger psoriatic phenotype.
['Simard|Mélissa|M|', 'Morin|Sophie|S|', 'Rioux|Geneviève|G|', 'Séguin|Rachelle|R|', 'Loing|Estelle|E|', 'Pouliot|Roxane|R|0000-0002-2423-9599']
D000262:Adenylyl Cyclases D002772:Cholera Toxin D000242:Cyclic AMP D004817:Epidermis D005260:Female D000091344:Filaggrin Proteins D006801:Humans D007545:Isoproterenol D008297:Male D008875:Middle Aged D008954:Models, Biological D011565:Psoriasis D015290:Second Messenger Systems D023822:Tissue Engineering
psoriasis cholera toxin isoproterenol tissue engineering cyclic adenosine monophosphate