RESUMO
Human papillomavirus infection is one of the most common and most distressing cutaneous diseases in patients with HIV infection. It is also a common, and often therapeutically challenging, infection in individuals who are immunologically competent. A wide range of therapeutic options exists for treating cutaneous human papillomavirus infections, but none is uniformly effective. In this report we describe a man with HIV-1 infection and disfiguring facial verruca vulgaris who demonstrated complete clinical response to intravenous cidofovir. Our report provides further support for the use of intravenous cidofovir as therapy for treatment-resistant and/or widespread cutaneous human papillomavirus infection.
Assuntos
Antivirais/administração & dosagem , Citosina/análogos & derivados , Organofosfonatos/administração & dosagem , Infecções por Papillomavirus/tratamento farmacológico , Dermatopatias Virais/tratamento farmacológico , Adulto , Antivirais/uso terapêutico , Cidofovir , Citosina/administração & dosagem , Citosina/uso terapêutico , Humanos , Injeções Intravenosas , Masculino , Organofosfonatos/uso terapêutico , Infecções por Papillomavirus/patologia , Dermatopatias Virais/patologia , Resultado do TratamentoRESUMO
VE-cadherin is an endothelial-specific cadherin that plays important roles in vascular morphogenesis and growth control. To investigate the mechanisms by which endothelial cells regulate cadherin cell surface levels, a VE-cadherin mutant containing the non-adhesive interleukin-2 (IL-2) receptor extracellular domain and the VE-cadherin cytoplasmic tail (IL-2R-VE-cadcyto) was expressed in microvascular endothelial cells. Expression of the IL-2R-VE-cadcyto mutant resulted in the internalization of endogenous VE-cadherin and in a dramatic decrease in endogenous VE-cadherin levels. The internalized VE-cadherin co-localized with early endosomes, and the lysosomal inhibitor chloroquine dramatically inhibited the down-regulation of VE-cadherin in cells expressing the IL-2R-VE-cadcyto mutant. Chloroquine treatment also resulted in the accumulation of a VE-cadherin fragment lacking the beta-catenin binding domain of the VE-cadherin cytoplasmic tail. The formation of the VE-cadherin fragment could be prevented by treating endothelial cells with proteasome inhibitors. Furthermore, inhibition of the proteasome prevented VE-cadherin internalization and inhibited the disruption of endothelial intercellular junctions by the IL-2RVE-cadcyto mutant. These results provide new insights into the mechanisms of VE-cadherin processing and degradation in microvascular endothelial cells.