Naschberger, E. et al. Increased expression of guanylate binding protein-1 in lesional skin of patients with cutaneous lupus erythematosus. Exp. Dermatol. 20, 102-106

Division of Molecular and Experimental Surgery, University Medical Center Erlangen, Erlangen, Germany.
Experimental Dermatology (Impact Factor: 3.76). 02/2011; 20(2):102-6. DOI: 10.1111/j.1600-0625.2010.01160.x
Source: PubMed


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.

Download full-text


Available from: Joerg Wenzel
    • " , 2008 ) . These activities have been linked to the ability of IFNs to phosphorylate STAT1 ( Zitzmann et al . , 2006 ) . High expression of ISGs such as CXCL9 , CXCL10 , MxA and GBP - 1 has been reported in interface dermatitis conditions such as cutaneous lupus erythematosus ( CLE ) and here increased expression is linked with disease severity ( Naschberger et al . , 2010 ; Wenzel et al . , 2005 ) ."
    [Show abstract] [Hide abstract]
    ABSTRACT: Interferon lambda (IFNλ) is important for epidermal defence against viruses. It is produced by, and acts on, keratinocytes, whereas fibroblasts were previously considered to be unresponsive to this type III IFN. Herein we report findings revealing cell type-specific differences in IFNλ signalling and function in skin resident cells. In dermal fibroblasts, IFNλ induced the expression of MxA, a potent antiviral factor, but not other IFN signature genes as it does in primary keratinocytes. In contrast to its effect on keratinocytes, IFNλ did not phosphorylate STAT1 in fibroblasts, but instead activated MAPKs. Accordingly, inhibition of MAPK activation (p38 and p42/44) blocked the expression of MxA protein in fibroblasts but not in keratinocytes. Functionally, IFNλ inhibited proliferation in keratinocytes but not in fibroblasts. Moreover, IFNλ upregulated the expression of TGFβ1-induced collagens in fibroblasts. Taken together, our findings identify primary human dermal fibroblasts as responder cells to IFNλ. Our study shows cutaneous cell type-specific IFN signalling and suggests that IFNλ, whilst important for epidermal anti-viral competence, may also have a regulatory role in the dermal compartment balancing type I IFN-induced inhibition of tissue repair processes.Journal of Investigative Dermatologyaccepted article preview online, 19 August 2015. doi:10.1038/jid.2015.317.
    No preview · Article · Aug 2015 · Journal of Investigative Dermatology
  • Source
    • "In accord with the proposed mechanism, inhibitors of TLR7 and TLR9 signaling in a lupus-prone murine model of interface dermatitis attenuated the skin lesions [88]. Moreover, a recently identified IFNα-and γ-induced protein—the GTPase human guanylate binding protein- 1 (GBP-1)—is expressed by keratinocytes and endothelial cells in primary and ultraviolet-(UV-) induced skin lesions from patients with various subtypes of CLE compared to nonlesional skin [89]. It has also been recently demonstrated that the IFNα-inducible IFI16 protein—normally localized in the nucleus—translocates in the cytoplasm of affected skin cells from lupus patients and in UV irradiated keratinocytes—leading to generation of antibodies against the IFNα-inducible IFI16 recently detected in sera of lupus patients [90] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target.
    Full-text · Article · Nov 2011 · BioMed Research International
  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical manifestations of cutaneous lupus erythematosus are diverse and different subtypes of the disease have been defined. It is characteristic for lupus skin inflammation that a significant activation of innate interferon pathways is observable. Endogenous molecules indicative for tissue damage (damage-associated molecular patterns [DAMPs]) show cytokine-like properties once released from intracellular compartments and these DAMPs have been shown to influence the course of inflammatory responses. Cytokines including TNF-αα and IL-1 family members significantly contribute to the chronic inflammatory phenotype and, in combination with DAMPs, impact on the activation of innate interferons. A better understanding of the deregulated cytokine network in cutaneous lupus erythematosus patients with distinct disease phenotypes and genetic backgrounds is of high importance and a prerequisite for recommending and developing more individualized therapeutic strategies.
    No preview · Article · Jul 2011 · Expert Review of Dermatology
Show more