BACKGROUND: The dogma in psoriasis is that due to pathogen-induced inflammatory responses, an autoreactive immune response is induced that leads to tissue destruction. However, this model might be too simplistic. Literature data suggest that the expression of enzymes crucial for fatty acid oxidation is upregulated in the skin of patients with psoriasis compared with healthy individuals. OBJECTIVES: To examine the influence of fatty acid oxidation on psoriasis with regard to expression and activity of the key enzyme in fatty acid oxidation, carnitine palmitoyltransferase-1 (CPT-1) and the effect of the CPT-1 inhibitor, Etomoxir. METHODS: Experiments were performed with homogenates of lesional and healthy skin, fibroblast cultures and a model of human psoriatic skin transplanted on immune-deficient BNX mice. RESULTS: CPT-1 was highly active in lesional skin. Etomoxir was able to block CPT-1 activity in skin, implying that this antagonist may have the potential to suppress psoriasis when administered topically. In the mouse model, Etomoxir had an antipsoriatic effect that was at least as good as that of betamethasone, as evidenced by reduction of epidermal thickness, keratinocyte proliferation and differentiation. CONCLUSIONS: We conclude that fatty acid metabolism and in particular CPT-1 may be an excellent target for treatment of psoriasis.
BACKGROUND: The dogma in psoriasis is that due to pathogen-induced inflammatory responses, an autoreactive immune response is induced that leads to tissue destruction. However, this model might be too simplistic. Literature data suggest that the expression of enzymes crucial for fatty acid oxidation is upregulated in the skin of patients with psoriasis compared with healthy individuals. OBJECTIVES: To examine the influence of fatty acid oxidation on psoriasis with regard to expression and activity of the key enzyme in fatty acid oxidation, carnitine palmitoyltransferase-1 (CPT-1) and the effect of the CPT-1 inhibitor, Etomoxir. METHODS: Experiments were performed with homogenates of lesional and healthy skin, fibroblast cultures and a model of human psoriatic skin transplanted on immune-deficient BNX mice. RESULTS:CPT-1 was highly active in lesional skin. Etomoxir was able to block CPT-1 activity in skin, implying that this antagonist may have the potential to suppress psoriasis when administered topically. In the mouse model, Etomoxir had an antipsoriatic effect that was at least as good as that of betamethasone, as evidenced by reduction of epidermal thickness, keratinocyte proliferation and differentiation. CONCLUSIONS: We conclude that fatty acid metabolism and in particular CPT-1 may be an excellent target for treatment of psoriasis.
Authors: Regina Ensenauer; Ralph Fingerhut; Sonja C Schriever; Barbara Fink; Marc Becker; Nina C Sellerer; Philipp Pagel; Andreas Kirschner; Torsten Dame; Bernhard Olgemöller; Wulf Röschinger; Adelbert A Roscher Journal: J Lipid Res Date: 2012-02-16 Impact factor: 5.922
Authors: Sara M Nowinski; Ashley Solmonson; Joyce E Rundhaug; Okkyung Rho; Jiyoon Cho; Cory U Lago; Christopher L Riley; Sunhee Lee; Shohei Kohno; Christine K Dao; Takeshi Nikawa; Shawn B Bratton; Casey W Wright; Susan M Fischer; John DiGiovanni; Edward M Mills Journal: Nat Commun Date: 2015-08-27 Impact factor: 14.919
Authors: Anne Skøttrup Mørkholt; Ove Wiborg; Jette G K Nieland; Søren Nielsen; John Dirk Nieland Journal: Sci Rep Date: 2017-05-19 Impact factor: 4.379