1. Thalidomide Improves Psoriasis-like Lesions and Inhibits Cutaneous VEGF Expression without Alteration of Microvessel Density in Imiquimod- induced Psoriatic Mouse Model.
- Author
-
Liu JH, Wu HH, Zhao YK, Wang F, Gao Q, and Luo DQ
- Subjects
- Acitretin pharmacology, Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Down-Regulation, Female, Mice, Inbred BALB C, Microvessels metabolism, Microvessels pathology, Psoriasis chemically induced, Psoriasis metabolism, Psoriasis pathology, Signal Transduction drug effects, Skin metabolism, Skin pathology, Vascular Endothelial Growth Factor A blood, Angiogenesis Inhibitors pharmacology, Imiquimod, Microvessels drug effects, Neovascularization, Pathologic, Psoriasis drug therapy, Skin blood supply, Skin drug effects, Thalidomide pharmacology, Vascular Endothelial Growth Factor A metabolism
- Abstract
Background: Psoriasis is a chronic inflammatory skin disorder of unknown etiology. Increasing evidence suggests that psoriasis is probably an angiogenesis-dependent disease. Thalidomide has been reported being able to inhibit the effects of fibroblast growth factor 2 and vascular endothelial growth factor (VEGF), and inhibit tumour necrosis factor-alpha synthesis, and suppress tumour necrosis factor-induced nuclear factor-kappa B activation in Jurkat cells, resulting in suppression of proliferation inflammation, angiogenesis, and the immune system, which are related to the pathogenesis of psoriasis., Objective: Our study evaluated the influence of thalidomide on the lesional alterations, VEGF expressions and angiogenesis in imiquimod-induced mouse model., Methods: Balb/c female mice (n=48) 8-12 weeks of age were randomly divided into 6 groups including negative control (vaseline cream), positive control (5% imiquimod cream), and experimental groups including low-dose (10 mg/kg.d), moderate-dose (30 mg/kg.d) and high-dose thalidomide (85 mg/kg.d), and acitretin group (6 mg/kg.d). Serum levels of VEGF-A were quantified by enzyme-linked immunosorbent assay. VEGF protein expression was measured by western blotting and the microvessel density by immunohistochemical staining., Results: The total psoriasis area and severity index scores in the moderate- and high-dose thalidomide and acitretin groups decreased significantly (p<0.001 for each), and so were the total Baker's scores in the high-dose thalidomide (p=0.008) and acitretin groups (p=0.021). The mean thickness of the epidermis in the experimental and acitretin groups decreased significantly, respectively (p<0.001 for all); the acitretin group was the thinnest. The cutaneous VEGF protein levels down-expressed significantly in the moderate- and high-dose thalidomide groups (p<0.05 for both), while those in the low-dose thalidomide and acitretin did not (p>0.05 for both). There were no differences for serum VEGF-A levels and the density of microvessels among the positive and experimental groups., Conclusion: Thalidomide can improve the psoriasis-like lesions and inhibit the expression of cutaneous VEGF in imiquimod-induced psoriatic model with dose-dependence, however, it does not alter circulating VEGF-A levels and microvessel density in dermis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2018
- Full Text
- View/download PDF