Psoriasiform skin disease in transgenic pigs with high-copy ectopic expression of human integrins α2 and β1.

Psoriasis is a complex human-specific disease characterized by perturbed keratinocyte proliferation and a pro-inflammatory environment in the skin. Porcine skin architecture and immunity are very similar to that in humans, rendering the pig a suitable animal model for studying the biology and treatment of psoriasis. Expression of integrins, which is normally confined to the basal layer of the epidermis, is maintained in suprabasal keratinocytes in psoriatic skin, modulating proliferation and differentiation as well as leukocyte infiltration.

Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment.

TNFα-, IL-23- and IL-17-targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin, the presence of Langerhans cells (LCs) is reduced, but the role of LC is poorly understood.

Leptin deficiency in mice counteracts imiquimod (IMQ)-induced psoriasis-like skin inflammation while leptin stimulation induces inflammation in human keratinocytes.

Leptin is an adipocyte-derived cytokine secreted mostly by adipose tissue. Serum leptin levels are elevated in obese individuals and correlate positively with body mass index (BMI). Interestingly, serum leptin levels are also elevated in patients with psoriasis and correlate positively with disease severity.

Exploring Valrubicin's Effect on Propionibacterium Acnes-Induced Skin Inflammation in Vitro and in Vivo.

Acne is a common skin disease involving colonization with Propionibacterium acnes (P. acnes), hyperproliferation of the follicular epithelium and inflammatory events. Valrubicin is a second-generation anthracycline, non-toxic upon contact, and available in a topical formulation.

Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin.

Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for the treatment of skin diseases. Although we have previously documented potent lentiviral gene delivery to human skin, vectors based on adeno-associated virus (AAV) rank among the most promising gene delivery tools for in vivo purposes. Thus, we compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin in a xenotransplanted mouse model.

Debio 0932, a new oral Hsp90 inhibitor, alleviates psoriasis in a xenograft transplantation model.

Debio 0932 is a novel oral heat shock protein 90 (Hsp90) inhibitor developed for anti-cancer therapy. Surprising-ly, during the first clinical trial, one psoriasis patient experienced complete remission of his skin manifestation. However, a possible therapeutic utility of Hsp90 in psoriasis has not previously been reported.

Valrubicin activates PKCa in keratinocytes: a conceivable mode of action in treating hyper-proliferative skin diseases.

Background: Valrubicin is a semisynthetic anthracycline developed as an anti-cancer drug able to ameliorate psoriasis and non-melanoma skin cancer (NMSC) by topical application in animal models. Valrubicin decreases cell proliferation, and induces apoptosis; however its mode of action is still unknown. Valrubicin localizes in the cytoplasm and its valerate moiety resembles diacylglycerol, an activator of protein kinase C (PKC) α, which belongs to the PKC family of cytoplasmic serine/threonine protein kinases.

A lentiviral vector-based genetic sensor system for comparative analysis of permeability and activity of vitamin D3 analogues in xenotransplanted human skin.

Vitamin D3 analogues are widely used topical and oral remedies for various ailments such as psoriasis, osteoporosis and secondary hyperparathyroidism. In topical treatment, high skin permeability and cellular uptake are key criteria for beneficial effects due to the natural barrier properties of skin. In this study, we wish to establish an in vivo model that allows the comparison of permeability and activity of vitamin D3 analogues in human skin.

Resolution of psoriasis by a leukocyte-targeting bacterial protein in a humanized mouse model.

Psoriasis is a very common chronic skin disease, affecting 2-3% of the world's population or more than 125 million individuals worldwide. The characteristic lesion of psoriasis is due to rapid proliferation and shortened transition of keratinocytes through the epidermis. Proinflammatory white blood cells (WBCs) migrate into the psoriatic plaques, and the pathogenic cytokine environment causes the changes in keratinocyte proliferation and differentiation.

Statistical evaluation and experimental design of a psoriasis xenograft transplantation model treated with cyclosporin A.

Psoriasis xenograft transplantation models where human skin is transplanted onto immune-deficient mice are generally accepted in psoriasis research. Over the last decade, they have been widely employed to screen for new therapeutics with a potential anti-psoriatic effect. However, experimental designs differ in several parameters.

Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin.

Background: Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), and IL-23 for which monoclonal antibodies have already been approved for clinical use.

Topical application of valrubicin has a beneficial effect on developing skin tumors.

Valrubicin is a second generation anthracycline characterized by an excellent safety profile presenting no skin toxicity or necrosis upon contact. In its current liquid formulation (Valstar; Indevus Pharmaceuticals, Lexington, MA), it is approved solely for the treatment of bladder cancer. Recently, valrubicin was incorporated in a cream formulation rendering this drug available for topical application.

Valrubicin in a topical formulation treats psoriasis in a xenograft transplantation model.

Valrubicin is a cytostatic drug currently approved by the American Federal Drug Administration as a trademarked Valstar sterile solution for the treatment of bladder cancer. Valrubicin has shown an excellent therapeutic potential with minimal toxicity. This study investigated the effect in vivo of treating psoriasis with a daily topical application of valrubicin cream in a psoriasis xenograft transplantation model.

Amelioration of psoriasis by anti-TNF-alpha RNAi in the xenograft transplantation model.

Tumor necrosis factor-alpha (TNF-alpha) is upregulated in psoriatic skin and represents a prominent target in psoriasis treatment. The level of TNF-alpha-encoding mRNA, however, is not increased in psoriatic skin, and it remains unclear whether intervention strategies based on RNA interference (RNAi) are therapeutically relevant. To test this hypothesis the present study describes first the in vitro functional screening of a panel of short hairpin RNAs (shRNAs) targeting human TNF-alpha mRNA and, next, the transfer of the most potent TNF-alpha shRNA variant, as assessed in vitro, to human skin in the psoriasis xenograft transplantation model by the use of lentiviral vectors.

[Interleukin-20--a new target in psoriasis treatment].

Interleukin-20 (IL-20) is suggested as a new target in psoriasis treatment. It was first described in 2001, and the potential role of this cytokine in psoriasis was suggested because mice which were over-expressing IL-20 developed a psoriasis-like phenotype of the skin. Subsequently, IL-20 expression levels were found to be increased in psoriasis skin, and it was observed that these levels normalized upon psoriasis treatment.

Interleukin-20 as a target in psoriasis treatment.

Interleukin-20 (IL-20) is a new member of the IL-10 cytokine family discovered by a structural algorithm. IL-20 transgenic mice displayed skin abnormalities reminiscent of psoriasis, a finding that has prompted the investigation of this new interleukin in relation to this disease. This article reviews the role of IL-20 and its implication in psoriasis.

Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells.

Human bone marrow stromal cells (hMSCs) were stably transduced by a retroviral vector containing the gene for the catalytic subunit of human telomerase (hTERT). Transduced cells (hMSC-TERTs) had telomerase activity, and the mean telomere length was increased as compared with that of control cells. The transduced cells have now undergone more than 260 population doublings (PD) and continue to proliferate, whereas control cells underwent senescence-associated proliferation arrest after 26 PD.