Topical T3 enhances wound healing in guinea pigs, primarily by wound contraction. As this is a critical stage in healing of chronic ulcers, topical T3 could be a useful treatment for wounds.
Palmoplantar dermatoses have a tendency to be chronic and are frequently recalcitrant to treatment. We summarize our experience with paint PUVA in the treatment of 125 patients with palmoplantar dermatoses between the years 1996 and 2000. The dominant clinical picture of the lesions was hyperkeratosis in 84, pustulosis in 11 and exudative dermatitis in the remaining 30 patients. The treatment was applied thrice weekly on alternate days. The affected skin was painted with methoxsalen 0.1% solution, and exposed 30 minutes later to UVA radiation, starting at 0.25 J/cm(2), with increments of 0.25-0.50 J/cm(2) every third treatment. Complete response was considered if all signs disappeared, and partial response if improvement occurred in more than 75% of each of the clinical findings of scaling erythema, fissuring, pustule formation and infiltration. Sixty-nine percent of the patients had a good response (i.e. a complete or partial response), which was achieved in 78.5% of the exudative dermatitis lesions, but in only 46.7% of the pustular lesions. The average time to achieve good response was 13 weeks (range 1-42), with an average total dose of 50 J/cm(2) (range 0.50-366). Maintenance therapy every 1-4 weeks was recommended for all responding patients, but only 58 consented and were treated for an average period of 10 additional weeks. Side effects were minor and transient, mainly mild first-degree superficial skin burns in 10 patients, and patchy hyperpigmentation in three patients, which resolved after a few weeks.
Psoriasis is a chronic inflammatory skin disorder which results from pathological interactions between activated immunocytes and keratinocytes. Recent studies implicated the role of IL-17 and IL-22, secreted from Th17 and Th22 in the generation and propagation of the psoriatic plaque. Previously, we and others have shown that the expression of miR-197 is significantly decreased in psoriatic lesions. We further showed that miR-197 targets IL-22RA1 and that ectopic expression of miR-197 prevent IL-22 induced proliferation and migration of keratinocytes.Since the 3'UTR of the IL17RA subunit mRNA contains a putative binding site for miR-197, our aim was to expand our understanding of the miRNA-mediated crosstalk between immunocytes and keratinocytes by studying the effect of miR-197 expression on IL-17A signaling pathway. Luciferase reporter assays along with Western blot analysis revealed that miR-197 directly targets the 3'UTR of IL17RA. Furthermore, ectopic expression of miR-197 led to a significant decrease in IL-17A-induced expression of CCL20, a known downstream effector of IL-17A. Interestingly, the addition of IL-17A to keratinocytes led to a rapid and transient increase in the expression of miR-197. Chromatin immuno-precipitation assays showed that keratinocytes' treatment with IL-17 leads to C/EBP binding to the promoter region of miR-197, and that the expression level of miR-197 is directly proportional to the extent of C/EBP binding to the promoter. Moreover, following treatment with IL-17A, the histone acetylation pattern at the miR-197 promoter turns to become characteristic of transcribed chromatin.Taken together, our results suggest that a positive-negative feedback loop exists between IL-17A and miR-197 in keratinocytes; the cytokine induces the binding of C/EBPα to miR-197 promoter sequences, enhances miR-197 expression that negatively attenuates IL-17 receptor and decreases the input along the IL-17A pathway. Our work suggests that in psoriasis, decreased expression of miR-197 may prevent the miR-197-induced attenuation of the IL-17 cascade, leading to its over-activity.
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