Thalidomide Improves Psoriasis-like Lesions and Inhibits Cutaneous VEGF Expression without Alteration of Microvessel Density in Imiquimod- induced Psoriatic Mouse Model

• Published in: Current vascular pharmacology Vol. 16; no. 5; p. 510
• Main Authors: Liu, Juan-Hua, Wu, Hui-Hui, Zhao, Yu-Kun, Wang, Fang, Gao, Qian, Luo, Di-Qing
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2018
• Subjects: Acitretin - pharmacology; Angiogenesis Inhibitors - pharmacology; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Female; Imiquimod; Mice, Inbred BALB C; Microvessels - drug effects; Microvessels - metabolism; Microvessels - pathology; Neovascularization, Pathologic; Psoriasis - chemically induced; Psoriasis - drug therapy; Psoriasis - metabolism; Psoriasis - pathology; Signal Transduction - drug effects; Skin - blood supply; Skin - drug effects; Skin - metabolism; Skin - pathology; Thalidomide - pharmacology; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor A - metabolism; pathological change; psoriasis model; Balb/c mice; thalidomide; VEGF; imiquimod
• ISSN: 1875-6212
• DOI: 10.2174/1570161115666171004123428

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. Our study evaluated the influence of thalidomide on the lesional alterations, VEGF expressions and angiogenesis in imiquimod-induced mouse model. 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. 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. 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.