Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function

Gorjão, Renata; Verlengia, Rozângela; Lima, Thaís Martins de; Soriano, Francisco Garcia; Cury-Boaventura, Maria Fernanda; Kanunfre, Carla Cristine; Peres, Cleto Kaveski; Sampaio, Sandra Coccuzzo; Otton, Rosemari; Folador, Alessandra; Martins, Edgair Fernandes; Curi, Tânia Cristina Pithon; Portiolli, Érica Paula; Newsholme, Philip; Curi, Rui

doi:10.1016/j.clnu.2006.03.004

Cited by 78 publications

(71 citation statements)

References 60 publications

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“…Other studies have shown that different n-3 FAs can exert divergent effects on immune response. DHA-rich fish oil caused an increase in neutrophil and monocyte phagocytosis (48), whereas others demonstrated that EPA-rich fish oil did not alter this cell function (49). Verlengia et al (50) showed that the effect of EPA on gene expression in a human B-lymphocyte cell line (Raji) was more pronounced (25.9% of genes investigated were altered) compared with that of DHA (8.4% of genes investigated were altered).…”

Section: Discussionmentioning

confidence: 99%

Regulation of interleukin-2 signaling by fatty acids in human lymphocytes

Gorjão

Hirabara

Lima

et al. 2007

Journal of Lipid Research

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Docosahexaenoic (DHA; C22:6 n-3), eicosapentaenoic (EPA; C20:5 n-3), palmitic (PA; C16:0), and stearic (SA; C18:0) acids decrease lymphocyte proliferation in concentrations of .50 mM, as observed in our previous study. However, oleic acid (OA; C18:1 n-9) and linoleic acid (LA; C18:2 n-6) increase lymphocyte proliferation at 25 mM. In this study, the effect of these FAs on the interleukin-2 (IL-2) signaling pathway in human lymphocytes was investigated. Cells were isolated from heparinized venous blood of healthy human donors by density-gradient sedimentation. Cells were stimulated with 5 mg/ml concanavalin A and treated with FAs in the absence or presence of IL-2 for 1 hour. CD25-a externalization was analyzed by flow cytometry, and Janus kinase 1 ( JAK1), JAK3, signal transducer and activator of transcription (STAT) 5, extracellular signalregulated kinases (ERKs) 1 and 2, Akt, and protein kinase C (PKC)-Z phosphorylation were analyzed by Western blotting. The expression of CD25-a at the cell surface was increased by DHA, SA, and PA but was unaffected by EPA, OA, and LA. PA, SA, DHA, and EPA decreased JAK1, JAK3, STAT5, 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 FAs caused a marked decrease. PKC-Z phosphorylation was decreased by OA and LA and was not altered by the remaining FAs. In conclusion, the inhibitory effect of PA, SA, DHA, and EPA on lymphocyte proliferation observed in our previous study was attributable to a decrease in JAK/STAT, ERK, and Akt pathways activated by IL-2. Probably, OA and LA stimulated lymphocyte proliferation by increasing ERK1/2 phosphorylation through PKC-Z activation. The inhibition of JAK1, JAK3, STAT5, ERK1/2, and Akt phosphorylation caused by DHA, SA, and PA is associated with an alteration of CD25 expression at the cell surface.-Gorjão, R., S. M. Hirabara, T. M. de Lima, M. F. Cury-Boaventura, and R. Curi. Regulation of interleukin-2 signaling by fatty acids in human lymphocytes. J. Lipid Res.

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Section: Discussionmentioning

confidence: 99%

Regulation of interleukin-2 signaling by fatty acids in human lymphocytes

Gorjão

Hirabara

Lima

et al. 2007

Journal of Lipid Research

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“…Consequently, it could not be excluded that the increased incorporation of DHA in neutrophil lipids and the subsequent production of LT observed for each dose of DHA may also reflect the effect of cumulative doses of DHA. Results from human studies indeed indicate that the level of DHA reached a plateau after 18 weeks of dietary supplementation (18) and most of the published data reported longer supplementation periods (from 3 weeks to 6 months (5,6,8,9,13) ). However, the present data suggest that changes in total lipid content occurred within 2 weeks and therefore earlier than that reported until now.…”

Section: Discussionmentioning

confidence: 96%

Effect of dietary supplementation with increasing doses of docosahexaenoic acid on neutrophil lipid composition and leukotriene production in human healthy volunteers

et al. 2008

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n-3 PUFA supplementation helps in the prevention or treatment of inflammatory diseases and CVD. However, many supplementations reported so far are either a combination of n-3 PUFA or used large daily amounts of n-3 PUFA dosages. The present study investigated the influence of increasing dose intake of DHA on the fatty acid composition of phospholipids in neutrophils and on their capability to produce leukotrienes (LT) B4 and B5in vitro. Twelve healthy volunteers were supplemented with increasing daily doses of DHA (200, 400, 800 and 1600 mg, each dose in TAG containing DHA as the only PUFA and for a 2-week period). At the end of each supplementation period, neutrophil fatty acid composition, and LTB4 and LTB5 production were determined by GC and liquid chromatography–tandem MS, respectively. The DHA/arachidonic acid ratio increased in a dose-dependent manner with respect to the increasing doses of DHA supplementation and was significantly different from baseline after supplementation with either 400, 800 or 1600 mg DHA. The LTB5/LTB4 ratio was significantly increased compared to baseline after supplementation with 800 and 1600 mg DHA. LTB5/LTB4 and DHA/arachidonic acid ratios were correlated (r 0·531, P < 0·0001). The present data suggest that both changes in neutrophil lipid composition and LT production occurred with daily supplementation with 800 and 1600 mg DHA. The clinical benefits associated with these doses of DHA in inflammatory diseases remain to be investigated.

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“…O ensaio de migração quimiotática foi efetuado segundo adaptação do método de Boyden (1962), anteriormente utilizado em estudos in vivo, in vitro e ex vivo em nosso laboratório (Waitzberg et al, 1997;Waitzberg et al, 1996;Bellinati-Pires et al, 1992) e também amplamente utilizado por outros pesquisadores (Gorjão et al, 2006;Buenestado et al, 2006;Sperling et al, 1993;Turner et al, 1975).…”

Section: Do Ensaio De Quimiotaxiaunclassified

“…Existem diferentes maneiras de se avaliar a quimiotaxia, como o número ou porcentagem de células que migraram para o compartimento inferior da câmara (Gorjão et al, 2006;Wanten et al, 2000), ou pela distância percorrida pelos leucócitos no interior da membrana de celulose, que foi o método adotado na presente pesquisa (Buenestado et al, 2006;BellinatiPires et al, 1992).…”

Section: Do Ensaio De Quimiotaxiaunclassified

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Efeito de emulsão lipídica parenteral composta por mistura de triglicérides de cadeia média e óleos de soja, oliva e peixe sobre a migração e fagocitose de leucócitos de ratos

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Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function

Cited by 78 publications

References 60 publications

Regulation of interleukin-2 signaling by fatty acids in human lymphocytes

Regulation of interleukin-2 signaling by fatty acids in human lymphocytes

Effect of dietary supplementation with increasing doses of docosahexaenoic acid on neutrophil lipid composition and leukotriene production in human healthy volunteers

Efeito de emulsão lipídica parenteral composta por mistura de triglicérides de cadeia média e óleos de soja, oliva e peixe sobre a migração e fagocitose de leucócitos de ratos

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