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ARGINASE I, POLYAMINE, AND PROSTAGLANDIN E2 PATHWAYS SUPPRESS THE INFLAMMATORY RESPONSE AND CONTRIBUTE TO DIFFUSE CUTANEOUS LEISHMANIASIS
Diffuse cutaneous leishmaniasis
Arginase I
Ornithine decarboxylase
Prostaglandin
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
Author
Affilliation
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 β (TGF-β), 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-β 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.
Keywords
Leishmania amazonensisDiffuse cutaneous leishmaniasis
Arginase I
Ornithine decarboxylase
Prostaglandin
DeCS
Arginase/genéticaDinoprostona/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
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