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Arginase I, polyamine, and prostaglandin E2 pathways suppress the inflammatory response and contribute to diffuse cutaneous leishmaniasis.

By Jaqueline França Costa, Johan Jozef Rosa Maria Van Weyenbergh, Viviane Sampaio Boaventura de Oliveira, Nívea Faria Luz, Hayna Malta Santos, Murilo Cezar Souza Oliveira, Daniela Conceição Santos de Campos, Ana Cristina Saldanha, Washington Luis Conrado dos-Santos, Patrícia Torres Bozza, Manoel Barral Netto, Aldina Maria Prado Barral, Jackson Mauricio Lopes Costa and Valeria de Matos Borges

Abstract

Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of tegumentary leishmaniasis. The molecular mechanisms underlying DCL pathogenesis remain unclear, and there is no efficient treatment available. This study investigated the systemic and in situ expression of the inflammatory response that might contribute to suppression in DCL. The plasma levels of arginase I, ornithine decarboxylase (ODC), transforming growth factor ß (TGF-ß), and prostaglandin E2 (PGE2) were higher in patients with DCL, compared with patients with localized cutaneous leishmaniasis (LCL) or with controls from an area of endemicity. In situ transcriptomic analyses reinforced the association between arginase I expression and enzymes involved in prostaglandin and polyamine synthesis. Immunohistochemistry confirmed that arginase I, ODC, and cyclooxygenase2 expression was higher in lesion biopsy specimens from patients with DCL than in those from patients with LCL. Inhibition of arginase I or ODC abrogates L. amazonensis replication in infected human macrophages. Our data implicate arginase I, ODC, PGE2, and TGF-ß in the failure to mount an efficient immune response and suggest perspectives in the development of new strategies for therapeutic intervention for patients with DCL

Topics: Leishmania amazonensis, Diffuse cutaneous leishmaniasis, Arginase I, Ornithine decarboxylase, Prostaglandin E2, TGF-β, Arginase/genética, Dinoprostona/genética, Inflamação/genética, Leishmaniose Tegumentar Difusa/genética, Poliaminas/metabolismo, Adolescente, Adulto, Idoso, Arginase/sangue, Criança, Pré-Escolar, Dinoprostona/sangue, Feminino, Humanos, Inflamação/sangue, Leishmaniose Tegumentar Difusa/sangue, Masculino, Meia-Idade, Ornitina Descarboxilase/sangue, Poliaminas/sangue, Transdução de Sinal/genética, Fator de Crescimento Transformador beta/sangue
Publisher: Oxford University Press
Year: 2015
OAI identifier: oai:agregador.ibict.br.RI_FIOCRUZ:oai:localhost:icict/10638
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