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ABSTRACT: There is increasing evidence that selected peptide fragments of the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) have preserved immunomodulatory effects in various in vitro and in vivo models. However, until recently, emphasis has been attributed mostly to peptides related to the central pharmacophore of alpha-MSH (6-9) as well as to peptides homologous to the C-terminal tripeptide sequence, MSH (11-13). Here we investigated in detail the in vitro effects of an alpha MSH (11-13) derivative, K(D)PT, in which the last amino acid valine of alpha-MSH (11-13) was substituted by threonine and by the D-enantiomer of proline in position 2. Using the immortalized human sebocyte cell line SZ95 as an in vitro model we demonstrate that K(D)PDT has potent antagonistic effects against interleukin (IL)-induced activation of NF-kB presumably by inhibiting IkBalpha protein degradation. In contrast IL-1-mediated activation of the stress kinase p38 was not affected. The significance of the NF-kB-modulatory effect of K(D)PT was highlighted by suppression of IL-1-mediated mRNA expression and protein secretion of IL-6 and IL-8, two proinflammatory cytokines crucially implicated in the pathogenesis of acne vulgaris. Interestingly, K(D)PT likewise suppressed P. acnes-induced expression of IL-6 and IL-8. Our in vitro data are promising towards the therapeutic exploitation of small peptide derivatives of the C-terminal domain of alpha-MSH, e.g. K(D)PT, not only for the treatment of acne but also for many other inflammatory skin diseases.
Experimental Dermatology 08/2008; 17(7):630. · 3.54 Impact Factor
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ABSTRACT: Vitiligo is an acquired depigmenting disease with uncertain aetiopathogenesis, possibly associated with oxidative stress. Narrowband ultraviolet B phototherapy (NB-UVB) is the most widely used and effective treatment.
To evaluate the clinical effectiveness of NB-UVB and the repairing of oxidative stress-induced damage, using oral supplementation with an antioxidant pool (AP).
Patients (n = 35) with nonsegmental vitiligo were enrolled in a randomized, double-blind, placebo-controlled multicentre trial. The treatment group received, for 2 months before and for 6 months during the NB-UVB treatment, a balanced AP containing alpha-lipoic acid, vitamins C and E, and polyunsaturated fatty acids. The area and number of lesions, as well as some parameters of the oxidation-reduction (redox) status of the peripheral blood mononuclear cells (PBMCs) were estimated at the beginning, after 2 months, and at the end of the trial.
In total, 28 patients completed the study. After 2 months of AP supplementation, the catalase activity and the production of reactive oxygen species (ROS) were 121% and 57% of the basal values (P < 0.05 and P < 0.02 vs. placebo, respectively). The AP increased the therapeutic success of NB-UVB, with 47% of the patients obtaining > 75% repigmentation vs. 18% in the placebo group (P < 0.05). An increase in catalase activity to 114% (P < 0.05 vs. placebo) and decrease in ROS level of up to 60% (P < 0.02 vs. placebo) of the basal value was observed in PBMCs. Finally, the AP intake maintained the membrane lipid ratio (saturated : unsaturated fatty acids 1.8 : 3.1; P < 0.05), counteracting phototherapy-induced saturation.
Oral supplementation with AP containing alpha-lipoic acid before and during NB-UVB significantly improves the clinical effectiveness of NB-UVB, reducing vitiligo-associated oxidative stress.
Clinical and Experimental Dermatology 11/2007; 32(6):631-6. · 1.20 Impact Factor
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ABSTRACT: Psoriasis is a multifactorial skin dermatosis characterized in its classical form by erythematous and hyperkeratotic plaques on extensor surfaces of the body, that in most cases can be managed therapeutically by topical agents. Hyperproliferation and a marked inflammation in both epidermis and dermis are thought to be driven by interaction of activated type-1 T lymphocytes and antigen-presenting cells and keratinocytes that release several proinflammatory and immunomodulating molecules. The aim of this study is to investigate whether tetrabromofluorecin, commonly know as eosin, a classical compound traditionally topically used in psoriasis for its presumed anti-inflammatory activities, is able to modulate the production of TNF-alpha, IL-6 and IL-8 that are recognized as the most active and characterized cytokines in the pathogenesis of this skin disorder. HaCaT cell line was used to verify the effects on epidermal inflammation by eosin at scalar doses after testing the viability of cells. Two different population of cells, one stimulated by IFNgamma and one non-stimulated, were cultivated in presence of tolerable concentrations. The expression and release of IL-6, IL-8, IL-10, and TNF-alpha were analysed by RT-PCR and ELISA, respectively. Our results show that tolerable concentrations of eosin were 0.05%, 0.02%, and 0.01%. The expression and production of TNFalpha, IL-8 and IL-6 were dramatically reduced in presence of eosin 0.05% and 0.02% and the action of eosin was more pronounced on TNF-alpha. In agreement with clinical data, our results show that in presence of tolerable concentrations, eosin seems to influence remarkably the production of three important cytokines involved in the hyperproliferation and inflammatory process, giving a specific explanation of its efficacy and supporting its topical use in the clinical setting.
International journal of immunopathology and pharmacology 22(4):1067-75. · 2.99 Impact Factor
