RESUMEN
Psoriasis is a chronic, recurrent, heterogeneous, cutaneous inflammatory skin disease for which there is no cure. It affects approximately 7.5 million people in the United States. Currently, several biologic agents that target different molecules implicated in the pathogenic processes of psoriasis are being assessed in diverse clinical studies. However, relapse usually occurs within weeks or months, meaning there is currently no cure for psoriasis. Therefore, recent studies have discovered diverse new potential treatments for psoriasis: inhibitors of bacteria such as Staphylococcus aureus, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and neuropilin 1 (NRP1). A promising approach that has recently been described involves modifying antimicrobial peptides to develop new cutaneous anti-bacterial agents that target inflammatory skin disease induced by Staphylococcus. Increased expression of TRAIL and its death receptors DR4 and DR5 has been implicated in the pathogenesis of plaque psoriasis. In addition, TRAIL has the ability to inhibit angiogenesis by inducing endothelial cell death and by negative regulation of VEGF-induced angiogenesis via caspase-8-mediated enzymatic and non-enzymatic functions. Since NRP1 regulates angiogenesis induced by multiple signals, including VEGF, ECM and semaphorins, and also initiates proliferation of keratinocytes through NF-κB signaling pathway in involved psoriatic skin, targeting NRP1 pathways may offer numerous windows for intervention in psoriasis. In this review, we will focus on the current knowledge about the emerging role of synthetic antimicrobial peptides, TRAIL and NRP1 blocking peptides in the pathogenesis and treatment of psoriasis.
Asunto(s)
Antibacterianos , Bacterias , Factores Biológicos , Células Endoteliales , Queratinocitos , Necrosis , Neuropilina-1 , Péptidos , Psoriasis , Receptores de Muerte Celular , Recurrencia , Semaforinas , Piel , Enfermedades de la Piel , Staphylococcus , Staphylococcus aureus , Usos Terapéuticos , Ligando Inductor de Apoptosis Relacionado con TNF , Estados Unidos , Factor A de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation. However, the endogenous modulators for mast cell activation and the underlying mechanism have yet to be elucidated. Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation. OBJECTIVE: In order to investigate the effect of cannabinoid receptor-1 (CB1R) agonists on mast cell activation, AEA-derived compounds were newly synthesized and evaluated for their effect on mast cell activation. METHODS: The effects of selected compounds on FcepsilonRI-induced histamine and beta-hexosaminidase release were evaluated in a rat basophilic leukemia cell line (RBL-2H3). To further investigate the inhibitory effects of CB1R agonist in vivo, an oxazolone-induced atopic dermatitis mouse model was exploited. RESULTS: We found that CB1R inhibited the release of inflammatory mediators without causing cytotoxicity in RBL-2H3 cells and that CB1R agonists markedly and dose-dependently suppressed mast cell proliferation indicating that CB1R plays an important role in modulating antigen-dependent immunoglobulin E (IgE)-mediated mast cell activation. We also found that topical application of CB1R agonists suppressed the recruitment of mast cells into the skin and reduced the level of blood histamine. CONCLUSION: Our results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis.
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Animales , Ratones , Ratas , Basófilos , beta-N-Acetilhexosaminidasas , Agonistas de Receptores de Cannabinoides , Cannabinoides , Línea Celular , Citocinas , Dermatitis Atópica , Dermatitis por Contacto , Histamina , Inmunoglobulina E , Inmunoglobulinas , Inflamación , Interleucinas , Leucemia , Mastocitos , Péptido Hidrolasas , Psoriasis , Piel , Factor de Necrosis Tumoral alfaRESUMEN
No abstract available.
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BACKGROUND: Treatments including intralesional corticosteroid injection, pressure therapy, cryotherapy, and various laser therapies have had limited success for keloids and hypertrophic scars. OBJECTIVE: This trial evaluated the efficacy of a combination of 578 nm copper bromide laser and the more traditional intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with respect to scar color. METHODS: Keloids or hypertrophic scars of 12 Korean patients were treated five times by the combined treatment at 4-week intervals. Clinical improvement was assessed by the physicians' global assessment (PGA) comparing pre- and post-treatment photographs, as well as 4 weeks after the last treatment. Erythema intensity was quantified using a mexameter. RESULTS: Most scars showed significant clinical improvement in PGA and decreased erythema intensity after 5 treatments. All patients showed improvements in symptoms like pruritus. CONCLUSION: The combined treatment is effective for keloids and hypertrophic scars, especially when the telangiectatic portion of the scars is prominent. The adjunctive use of 578 nm copper bromide laser decreased the telangiectatic side effects of an intralesional corticosteroid injection by reducing the vascular components of scars.
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Humanos , Cicatriz , Cicatriz Hipertrófica , Cobre , Crioterapia , Eritema , Queloide , Terapia por Láser , Proyectos Piloto , PruritoRESUMEN
Pilar sheath acanthoma is a rare, benign follicular hamartoma that commonly affects middle aged and elderly patients. Clinically, solitary, asymptomatic, skin-colored nodules with a central pore-like opening are seen for more than one year. As a consequence of the histology, pilar sheath acanthoma should be differentiated from trichofolliculoma and dilated pore of Winer. We report here on a case of pilar sheath acanthomas that presented as asymptomatic solitary skin colored nodules on both cheeks.