FIGURE 7.

Valpha alleviates inflammation in a mouse model of psoriasis by normalizing the hyperplastic epidermis and vascular abnormalities. A, experimental scheme of a TPA-induced psoriasis model using keratin 14-VEGF-A mice for two periods: one includes five topical application of 0.02% TPA to both sides of the ear for 2 weeks (induction period), and one includes treatment with each indicated protein twice a week for 2 weeks (treatment period). TPA was applied during the treatment period as well as the induction period. D, day. B–D, after generation of TPA-induced psoriasis, mouse ears were examined. B, the gross appearance of TPA-treated ears at the end of the study (a 2-week induction period followed by a 2-week treatment period using each indicated protein) showed prominently enlarged hyperplastic blood vessels on the erythematous and scaly ear skin of Fc-treated mice, whereas VEGF-Trap-, Enbrel-, or Valpha-treated mice showed lower degrees of inflammatory signs. C, hematoxylin/eosin staining of TPA-treated ears revealed that, compared with Fc-treated mice, which showed psoriasis-like histological changes such as acanthosis, parakeratosis, and mixed inflammatory infiltrates, VEGF-Trap-, Enbrel-, or Valpha-treated mice showed significant improvements in these phenotypes. Scale bars = 200 μm. D, immunofluorescence analysis using anti-CD31 (red) and anti-LYVE-1 (green) antibodies showed blood and lymphatic vessels, respectively, after treatment with each indicated protein. Scale bars = 100 μm. E–G, quantification analyses of ear thickness (in micrometers), blood vessel (BV) area (percent), and lymphatic vessel (LV) area (%). Bars represent means ± S.D. (n = 3). *, p < 0.05 versus Fc; #, p < 0.05 versus Enbrel. VT, VEGF-Trap; Enb, Enbrel; Val, Valpha.