Increased expression of guanylate binding protein-1 in lesional skin of patients with cutaneous lupus erythematosus.

Division of Molecular and Experimental Surgery, University Medical Center Erlangen, Erlangen, Germany.
Experimental Dermatology (Impact Factor: 3.58). 02/2011; 20(2):102-6. DOI: 10.1111/j.1600-0625.2010.01160.x
Source: PubMed

ABSTRACT The large GTPase human guanylate binding protein-1 (GBP-1) is a key mediator of angiostatic effects of inflammation and is induced by interferon (IFN)-α and IFN-γ in endothelial cells (ECs). The aim of this study was to investigate whether GBP-1 is a marker of skin lesions in patients with cutaneous lupus erythematosus (CLE). Western blotting revealed that GBP-1 was in vitro induced by IFN-α and -γ in primary keratinocytes obtained from healthy controls. Moreover, we found that this protein was expressed by keratinocytes and ECs in primary and ultraviolet (UV)-induced skin lesions from patients with various subtypes of CLE, when compared to non-lesional skin. No GBP-1 expression was noted in skin biopsy specimens 24 or 72 h after UV irradiation prior to lesion formation in patients with CLE or in healthy control specimens with or without UV irradiation. Initial findings suggest that GBP-1 is not expressed in other skin diseases with different inflammatory aetiology, such as atopic dermatitis. We conclude that GBP-1 expression is closely associated with skin lesions in patients with CLE, suggesting a contribution of GBP-1 in the pathogenesis of this disease.

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    ABSTRACT: Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease. Different pathogenetic mechanisms, including the accumulation of apoptotic keratinocytes in CLE, have been reported. Therefore, we investigated whether CLE and other inflammatory skin diseases differ with regard to the epidermal expression of molecules that are crucial for the initiation and regulation of apoptosis. In this study, 241 skin biopsies from patients with CLE, psoriasis (PSO), lichen planus (LP) and healthy controls (HCs) were analysed immunohistochemically using the tissue microarray (TMA) technique. The TUNEL assay and anti-activated caspase-3 antibodies revealed a significant increase of apoptotic keratinocytes in CLE lesions compared with HCs. Furthermore, we detected a significant increase in the epidermal expression of CD95 in CLE specimens compared with PSO, LP and HCs. These data suggest that the accumulation of apoptotic keratinocytes in CLE might be due to the increased epidermal expression of CD95, resulting in increased activity of the extrinsic apoptotic pathway in the disease.
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    ABSTRACT: Cutaneous lupus erythematosus (CLE) denotes a heterogeneous spectrum of autoimmune diseases that primarily affect the skin. Ultraviolet irradiation (UV) is one of the most important environmental factors that can trigger skin lesions in CLE or even induce systemic organ manifestation. It has been shown that broad-spectrum sunscreen with high sun protection factors can effectively prevent UV-induced skin lesions in patients with different subtypes of CLE. In this issue of Experimental Dermatology, Zahn and colleagues demonstrate that potent photoprotection block disease-specific skin lesions in CLE patients by reducing lesional tissue damage and interferon-driven inflammation. This article is protected by copyright. All rights reserved.
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