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Doctoral Thesis
DOI
10.11606/T.42.2011.tde-09022012-134757
Document
Author
Full name
Mariane Tami Amano
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Câmara, Niels Olsen Saraiva (President)
Boscardin, Silvia Beatriz
Lima, Wothan Tavares de
Ramos, Marcela Sorelli Carneiro
Soriano, Francisco Garcia
Title in Portuguese
O papel da heme oxigenase-1 na modulação de células dendríticas levando à proteção da lesão por isquemia e reperfusão.
Keywords in Portuguese
Células dendríticas
Isquemia
Linfócitos
Rim
Abstract in Portuguese
A isquemia e reperfusão (IR) é a principal causa de insuficiência renal aguda. Evidências mostram a participação de linfócitos T e células dendríticas (DC) na lesão por IR. Entretanto, os mecanismos envolvidos não estão claros. A enzima heme oxigenase (HO)-1 está relacionada à diminuição de respostas inflamatórias. Neste trabalho, investigamos a participação de linfócitos T CD4+ e DC na proteção da lesão por IR induzida pela HO-1. Injetamos em camundongos um indutor de HO-1 (Hemin), e realizamos a IR. Avaliamos a lesão pela uréia e creatinina no soro, a expressão de citocinas por RT-PCR, nível de proteínas por bioplex e perfil celular por FACS. Observamos que a HO-1 protegeu da lesão por IR. A diminuição de INFg com a HO-1 sugeriu uma menor ativação de linfócitos T. No entanto, a transferência de células CD4+ tratadas com Hemin não apresentou diferença. Vimos que a HO-1 alterou o fenótipo das DC após IR e suprimiu a produção de TNFa pelas mesmas. Concluímos que a proteção pela HO-1 é capaz de modular a resposta inflamatória de DC, diminuindo o TNFa.
Title in English
The role of heme oxygenase-1 in dendritic cells modulation leading to ischemia and reperfusion injury protection.
Keywords in English
Dendritic cells
Ischemia
Kidney
Lymphocytes
Abstract in English
The ischemia and reperfusion (IR) is the main acute kidney injury. Evidences have shown the role of CD4+ T cells and dendritic cells (DC) in the IR injury. However, the mechanisms involved in the participation of these cells are not clear. The heme oxygenase (HO)-1 enzyme is associated to decrease in inflammatory responses. In this work, we investigated the role of CD4+ T cells and DC in renal injury protection induced by HO-1. We injected in mice a HO-1 inducer (Hemin), and we did the IR. Renal injury was evaluated by serum levels of urea and creatinine, cytokines expression by RT-PCR, proteins level by bioplex and cell profile by FACS. We observed that HO-1 lead to IR injury protection. The IFNg decrease with HO-1 suggested less T cells activation. However, transfer of hemin treated CD4+ cells did not differ from the other group. We observed that HO-1 altered DC phenotype after IR and suppressed TNFa production by these cells. We concluded that the protection by HO-1is able to modulate DC inflammatory response, diminishing TNFa.
 
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Publishing Date
2012-03-15
 
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