Albendazole negatively regulates keratinocyte proliferation.

Background . Increased keratinocyte proliferation occurs in the skin of psoriatic patients and is supposed to play a role in the pathogenesis of this disorder. Compounds interfering with keratinocyte proliferation could be useful in the management of psoriatic patients. AIM: To investigate whether albendazole, an anti-helmintic drug that regulates epithelial cell function in various systems, inhibits keratinocyte proliferation in models of psoriasis. METHODS: Aldara-treated mice received daily topical application of albendazole. Keratinocyte proliferation and keratin (K) 6 and K16 expression were evaluated by immunohistochemistry and Western blotting and inflammatory cells/mediators were analyzed by immunohistochemistry and real-time PCR. In human keratinocytes (HEKa andHaCaT) treated with albendazole, cell cycle and proliferation, keratins and cell cycle-associated factors were evaluated by flow cytometry, colorimetric assay and Western blotting respectively. RESULTS: Aldara-treated mice given albendazole exhibited reduced epidermal thickness, decreased number of proliferating keratinocytes and K6/K16 expression. Reduction of CD3- and Ly6G-positive cellsin the skin of albendazole-treated mice associated with inhibition of IL-6, TNF-a, IL-1beta, IL-17A, IL36, CCL17, CXCL1, CXCL2 and CXCL5 expression.Treatment of keratinocyteswith albendazole reduced K6/K16 expression and reversibly inhibited cell growth by promoting accumulation of cells in S-phase. This phenomenon was accompanied by down-regulation of CDC25A, a phosphatase regulating progression of cell cycle through S phase, and PKR-dependenthyper-phosphorylation of eIF2alpha, an inhibitor of CDC25 translation.In Aldara-treated mice, albendazole activated PKR, enhanced eIF2alpha phosphorylation and reduced CDC25A expression. CONCLUSIONS: Data show that albendazole inhibits keratinocyte proliferation and exerts therapeutic effect in a murine model of psoriasis.