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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Prostaglandins D-2 and E-2 have opposite effects on alveolar macrophages infected with Histoplasma capsulatum

Texto completo
Autor(es):
Pereira, Priscilla A. T. [1] ; Assis, Patricia A. [1] ; Prado, Morgana K. B. [1] ; Ramos, Simone G. [2] ; Aronoff, David M. [3] ; de Paula-Silva, Francisco W. G. [1] ; Sorgi, Carlos A. [1] ; Faccioli, Lucia H. [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pathol, BR-14040903 Ribeirao Preto, SP - Brazil
[3] Vanderbilt Univ, Med Ctr, Dept Med, Div Infect Dis, Nashville, TN 37232 - USA
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Journal of Lipid Research; v. 59, n. 2, p. 195-206, FEB 2018.
Citações Web of Science: 5
Resumo

Prostaglandin E2 (PGE(2)) suppresses macrophage effector mechanisms; however, little is known about the function of PGD(2) in infected alveolar macrophages (AMs). Using serum-opsonized Histoplasma capsulatum (Ops-H. capsulatum) in vitro, we demonstrated that AMs produced PGE(2) and PGD(2) in a time-dependent manner, with PGE(2) levels exceeding those of PGD(2) by 48 h postinfection. Comparison of the effects of both exogenous PGs on AMs revealed that PGD(2) increased phagocytosis and killing through the chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes receptor, whereas PGE(2) had opposite effects, through E prostanoid (EP) receptor 2 (EP2)/EP4-dependent mechanisms. Moreover, PGD(2) inhibited phospholipase C-gamma (PLC-gamma) phosphorylation, reduced IL-10 production, and increased leukotriene B4 receptor expression. In contrast, exogenous PGE(2) treatment reduced PLC-gamma phosphorylation, p38 and nuclear factor kappa B activation, TNF-alpha, H2O2, and leukotriene B4, but increased IL-1 beta. production. Using specific compounds to inhibit the synthesis of each PG in vitro and in vivo, we found that endogenous PGD(2) contributed to fungicidal mechanisms and controlled inflammation, whereas endogenous PGE(2) decreased phagocytosis and killing of the fungus and induced inflammation. These findings demonstrate that, although PGD(2) acts as an immunostimulatory mediator to control H. capsulatum infection, PGE(2) has immunosuppressive effects, and the balance between these two PGs may limit collateral immune damage at the expense of microbial containment. (AU)

Processo FAPESP: 14/07125-6 - Novos aspectos funcionais dos eicosanóides
Beneficiário:Lúcia Helena Faccioli
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 09/07169-5 - Mediadores lipídicos como reguladores da resposta imune
Beneficiário:Lúcia Helena Faccioli
Linha de fomento: Auxílio à Pesquisa - Temático