期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 50, 页码 21264-21269出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0907550106
关键词
activator protein-1; Jun proteins; epidermis; angiogenesis; G6-31 antibody
资金
- National Institutes of Health [CA69184]
- Swiss National Fund [3100A0-108207]
- Austrian Science Foundation [NFN S94-SP11]
- Commission of the European Communities [LSHC-CT-2005-518178]
- Banco Bilbao Vizcaya Argentaria (BBVA)-Foundation
- Boehringer Ingelheim Inc
Although, vascular remodeling is a hallmark of many chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, anti-vascular strategies to treat these conditions have received little attention to date. We investigated the anti-inflammatory activity of systemic blockade of VEGF-A by the inhibitory monoclonal antibody G6-31, employing a therapeutic trial in a mouse model of psoriasis. Simultaneous deletion of JunB and c-Jun (DKO*) in the epidermis of adult mice leads to a psoriasis-like phenotype with hyper-and parakeratosis and increased subepidermal vascularization. Moreover, an inflammatory infiltrate and elevated levels of cytokines/chemokines including TNF alpha, IL-1 alpha/beta, IL-6, and the innate immune mediators IL-22, IL-23, IL-23R, and IL-12p40 are detected. Here we show that anti-VEGF antibody treatment of mice already displaying disease symptoms resulted in an overall improvement of the psoriatic lesions leading to a reduction in the number of blood vessels and a significant decrease in the size of dermal blood and lymphatic vessels. Importantly, anti-VEGF-treated mice showed a pronounced reduction of inflammatory cells within the dermis and a normalization of epidermal differentiation. These results demonstrate that systemic blockade of VEGF by an inhibitory antibody might be used to treat patients who have inflammatory skin disorders such as psoriasis.
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