Back to Search
Start Over
Thalidomide Improves Psoriasis-like Lesions and Inhibits Cutaneous VEGF Expression without Alteration of Microvessel Density in Imiquimod- induced Psoriatic Mouse Model.
- Source :
-
Current vascular pharmacology [Curr Vasc Pharmacol] 2018; Vol. 16 (5), pp. 510-521. - Publication Year :
- 2018
-
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.<br />Objective: Our study evaluated the influence of thalidomide on the lesional alterations, VEGF expressions and angiogenesis in imiquimod-induced mouse model.<br />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.<br />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.<br />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.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1875-6212
- Volume :
- 16
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Current vascular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 28982338
- Full Text :
- https://doi.org/10.2174/1570161115666171004123428