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Arginase I, Polyamine, and Prostaglandin E₂ Pathways Suppress the Inflammatory Response and Contribute to Diffuse Cutaneous Leishmaniasis

França-Costa, Jaqueline ; Van Weyenbergh, Johan ; Boaventura, Viviane S. ; Luz, Nivea F. ; Malta-Santos, Hayna ; Oliveira, Murilo Cezar Souza ; de Campos, Daniela Conceição Santos ; Saldanha, Ana Cristina ; dos-Santos, Washington L. C. ; Bozza, Patrícia T. ; Barral-Netto, Manoel ; Barral, Aldina ; Costa, Jackson M. ; Borges, Valeria M.

The Journal of infectious diseases, 2015-02, Vol.211 (3), p.426-435 [Periódico revisado por pares]

United States: Oxford University Press

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Título:
Arginase I, Polyamine, and Prostaglandin E₂ Pathways Suppress the Inflammatory Response and Contribute to Diffuse Cutaneous Leishmaniasis
Autor: França-Costa, Jaqueline ; Van Weyenbergh, Johan ; Boaventura, Viviane S. ; Luz, Nivea F. ; Malta-Santos, Hayna ; Oliveira, Murilo Cezar Souza ; de Campos, Daniela Conceição Santos ; Saldanha, Ana Cristina ; dos-Santos, Washington L. C. ; Bozza, Patrícia T. ; Barral-Netto, Manoel ; Barral, Aldina ; Costa, Jackson M. ; Borges, Valeria M.
Assuntos: Adolescent ; Adult ; Aged ; Arginase - blood ; Arginase - genetics ; Child ; Child, Preschool ; Dinoprostone - blood ; Dinoprostone - genetics ; Female ; Humans ; Inflammation - blood ; Inflammation - genetics ; Leishmaniasis, Diffuse Cutaneous - blood ; Leishmaniasis, Diffuse Cutaneous - genetics ; Male ; Middle Aged ; Ornithine Decarboxylase - blood ; Ornithine Decarboxylase - genetics ; PARASITES ; Polyamines - blood ; Polyamines - metabolism ; Signal Transduction - genetics ; Transcriptome - genetics ; Transforming Growth Factor beta - blood ; Transforming Growth Factor beta - genetics ; Young Adult
É parte de: The Journal of infectious diseases, 2015-02, Vol.211 (3), p.426-435
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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 (PG E₂) 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.
Editor: United States: Oxford University Press
Idioma: Inglês

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Arginase I, Polyamine, and Prostaglandin E₂ Pathways Suppress the Inflammatory Response and Contribute to Diffuse Cutaneous Leishmaniasis

United States: Oxford University Press

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