Peroxisome proliferator-activated receptor agonists (PPARs): a promising prospect in the treatment of psoriasis and psoriatic arthritis

Abstract

Psoriasis is a polygenic, inflammatory and progressive disease, characterized by an abnormal differentiation and hyperproliferation of keratinocytes, associated with impaired immunologic activation and systemic disorders, while psoriatic arthritis is a chronic inflammatory articular disease. Pathophysiology of psoriasis comprises a dysfunction of the immune system cells with an interactive network between cells and cytokines supporting the initiation and perpetuation of disease and leading to inflammation of skin, enthesis and joints. Recent studies have shown an important role of systemic inflammation in the development of atherosclerosis. Corroborating these findings, patients with severe Psoriasis have marked incidence of psoriatic arthritis, cardiovascular diseases, hypertension, dyslipidemia, obesity and diabetes mellitus, showing an increased risk for acute myocardial infarction, which suggests that the condition is not restricted to the skin. Nuclear receptors are ligand-dependent transcription factors, whose activation affects genes that control vital processes. Among them the peroxisome proliferator-activated receptor is responsible for establishing the relationship between lipids, metabolic diseases and innate immunity. In the skin, peroxisome proliferator-activated receptors have an important effect in keratinocyte homeostasis, suggesting a role in diseases such as psoriasis. The peroxisome proliferator-activated receptors agonists represent a relevant source of research in the treatment of skin conditions, however more clinical studies are needed to define the potential response of these drugs in patients with psoriasis and psoriatic arthritis.

Higher bodily adiposity, fat intake, and cholesterol serum levels are associated with higher disease activity in psoriatic arthritis patients: is there a link among fat and skin and joint involvement?

“…Furthermore, patients with PsA and psoriasis share some other pathophysiological characteristics (neoangiogenesis, insulin uptake, adipogenesis, lipid metabolism, and immune and epidermal proliferation) [6][7][8] and genetic aspects, such as peroxisome proliferator activated receptor (PPAR) polymorphism. Altogether, they have been considered triggers of inflammatory disorders and immune cell activation [32,33].…”

The role of lipids in psoriasis

“…They have been shown to occur in three isoforms: PPAR-α, -β and -γ. PPARs are activated by FA and their derivatives, and they regulate the metabolism of carbohydrates, lipids and proteins, and inhibit atherogenesis and proliferation of diverse cells including keratinocytes. PPAR-α affects the elimination of cholesterol by macrophages, and inhibits the synthesis of proinflammatory cytokines, similarly to PPAR-β [9,50,51]. Psoriasis is accompanied by a reduced expression of PPAR-α and -γ, and an increased expression of PPAR-β.…”

“…An improvement in psoriatic lesions has been observed in diabetic patients treated with oral troglitazone and pioglitazone (PPAR-γ agonists) [52,53]. However, the efficacy of PPAR agonists used topically in psoriasis has not been demonstrated [50].…”

“…Zidentyfikowano ich trzy izoformy: PPAR-α, -β i -γ. Są one aktywowane przez FA i ich pochodne, regulują metabolizm węglowodanów, tłuszczów i białek, hamują aterogenezę oraz proliferację różnych komórek, w tym keratynocytów. PPAR-α wpływa na usuwanie cholesterolu przez makrofagi, hamuje syntezę cytokin prozapalnych, podobnie PPAR-β [9,50,51]. W łuszczycy ekspresja PPAR-α i -γ jest zmniejszona, a PPAR-β wzrasta.…”

“…Obserwowano poprawę zmian łuszczycowych u pacjentów z cukrzycą leczonych doustnie troglitazonem i pioglitazonem (agoniści PPAR-γ) [52,53]. Nie wykazano jednak skuteczności agonistów PPAR stosowanych miejscowo w łuszczycy [50].…”