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Doctoral Thesis
DOI
10.11606/T.42.2008.tde-15092008-134403
Document
Author
Full name
Renata Gorjão
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Curi, Rui (President)
Lottenberg, Ana Maria Pita
Negro, Sonia Jancar
Silva, Silvana Auxiliadora Bordin da
Soriano, Francisco Garcia
Title in Portuguese
Efeito dos ácidos graxos sobre a via de sinalização da interleucina-2 em linfócitos humanos.
Keywords in Portuguese
Ácidos graxos
Interleucina 2
Linfócitos
Lipid RAFT
Proliferação
Sinalização intracelular
Abstract in Portuguese
Neste estudo investigamos os efeitos dos ácidos graxos sobre a função e sinalização intracelular de linfócitos humanos. Os ácidos oléico (OA) e linoléico (LA), em baixas concentrações, estimularam a proliferação celular induzida pela IL-2 através do aumento da fosforilação da proteína PKC-Z que levou a um aumento da fosforilação de ERK 1/2. Já os ácidos palmítico (PA), esteárico (SA), DHA e EPA diminuíram a proliferação destas células e inibiram a fosforilação de JAK1 e 3, STAT5, ERK e Akt. Os resultados obtidos são sugestivos de que o efeito inibitório promovido por PA, SA, DHA e EPA sobre a proliferação de linfócitos ocorreu devido à diminuição da fosforilação de proteínas fundamentais para a proliferação celular. Por outro lado, OA e LA estimularam a proliferação de linfócitos aumentando a fosforilação de ERK 1/2 através da ativação de PKC-Z, efeito dependente da PI3K. O efeito inibitório promovido pelo DHA está associado a uma alteração na quantidade de lipid rafts na membrana plasmática nos quais o receptor de IL-2 está localizado.
Title in English
Regulation of IL-2 signaling by fatty acids in human lymphocytes.
Keywords in English
Fatty acids
Interleukin 2
Intracellular signaling
Lipid RAFT
Lymphocytes
Proliferation
Abstract in English
The effect of fatty acids (FA) on interleukin -2 (IL-2) signaling pathway in human lymphocytes was investigated. Docosahexaenoic (DHA), eicosapentaenoic (EPA), palmitic (PA) and stearic (SA) acids decreased lymphocyte proliferation in concentrations above 50 mM. However, oleic (OA) and linoleic (LA) acids increase lymphocyte proliferation at 25 mM. PA, SA, DHA and EPA decreased JAK 1, JAK 3, STAT 5 and AKT phosphorylation induced by IL-2 but OA and LA did not cause any effect. OA and LA increased ERK1/2 phosphorylation whereas the other FA caused a marked decrease. PKC-Z phosphorylation was decreased by OA and LA only. In conclusion, the inhibitory effect of PA, SA, DHA and EPA on lymphocyte proliferation observed in our previous study was due to a decrease in protein phosphorylation activated by IL-2. Probably, OA and LA stimulated lymphocyte proliferation by increasing ERK 1/2 phosphorylation throught PKC-Z activation. The inhibition of JAK 1, JAK3, STAT 5, ERK1/2 and Akt phosphorylation caused by DHA is associated to a decrease in membrane lipid rafts contend.
 
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Publishing Date
2008-10-03
 
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