RESUMO
To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP. Similarly, expression of heme oxygenases was followed in skin from vitiligo patients before and after PUVA treatment. Single and double immunostainings were used in combination with light and confocal microscopic analysis and Western blotting. Melanocyte expression of heme oxygenase 1 is upregulated, whereas heme oxygenase 2 is reduced in response to UV and 4-TBP. Upregulation of inducible heme oxygenase 1 was also observed in UV-treated explant cultures, in skin of successfully PUVA-treated patients and in melanocytes cultured from vitiligo non-lesional skin. Heme oxygenase encoding genes were subsequently cloned to study consequences of either gene product on cell viability, demonstrating that HO-1 but not HO-2 overexpression offers protection from stress-induced cell death in MTT assays. HO-1 expression by melanocytes may contribute to beneficial effects of UV treatment for vitiligo patients.
Assuntos
Heme Oxigenase-1/metabolismo , Melanócitos/enzimologia , Melanócitos/patologia , Vitiligo/enzimologia , Vitiligo/patologia , Antioxidantes/metabolismo , Sequência de Bases , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Morte Celular/efeitos da radiação , Células Cultivadas , Retículo Endoplasmático/enzimologia , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/genética , Humanos , Melanócitos/efeitos da radiação , Estresse Oxidativo , Terapia PUVA , RNA/genética , RNA/metabolismo , Raios Ultravioleta , Regulação para Cima/efeitos da radiação , Vitiligo/tratamento farmacológicoRESUMO
BACKGROUND: Several clinical and laboratory observations point to the possible microscopical affection of normal-looking skin in leprosy. OBJECTIVE: This study was carried out to verify the microscopical affection of apparently normal-looking skin in different types of leprosy. PATIENTS AND METHODS: The study included 50 patients with different clinical types of leprosy. Biopsies from both skin lesions and normal-looking skin were obtained from each patient and examined for microscopical evidence of leprosy. RESULTS: Microscopical affection of normal-looking skin was detected in 52% of our cases, with higher incidence of affection towards the lepromatous end of the disease. CONCLUSION: Our findings underscore that the incidence of microscopical affection of normal-looking skin in leprosy is much higher on the lepromatous end of the spectrum of leprosy than on the tuberculoid end; during treatment, the leprosy granulomas may disappear from the normal skin before the clinical lesions. Moreover, the microscopic picture of indeterminate leprosy can be observed in the normal-looking skin of patients with tuberculoid leprosy or lepromatous leprosy, and this description appears not to be confined to the entity known as indeterminate leprosy.
