Regulation of human lymphocyte proliferation by fatty acids

Gorjão, Renata; Cury-Boaventura, Maria Fernanda; Lima, Thaís Martins de; Curi, Rui

doi:10.1002/cbf.1388

Cited by 50 publications

(72 citation statements)

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“…Proteins related to IL-2R-activated pathways may be modulated by FAs, which could explain some of their immunomodulatory effects. We have shown previously that DHA, EPA, palmitic acid (PA), and stearic acid (SA) decreased the stimulatory effect of IL-2 on lymphocyte proliferation, increasing the percentage of cells in G 1 phase and decreasing the proportion of cells in S and G 2 /M phases after 48 h of treatment, whereas LA and oleic acid (OA) at low concentration (25 mM) caused an additive effect to IL-2, increasing cell proliferation (9).…”

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“…Fatty acids can control leukocyte functions such as cytokine production (7), macrophage phagocytosis (8), and lymphocyte proliferation (9). Some FAs (e.g., n-3) are gen-erally considered beneficial for human health because of their immunosuppressive effects in some autoimmune and inflammatory diseases (10)(11)(12).…”

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“…Some FAs (e.g., n-3) are gen-erally considered beneficial for human health because of their immunosuppressive effects in some autoimmune and inflammatory diseases (10)(11)(12). The n-3 FAs eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3) cause a marked decrease in lymphocyte proliferation at 50 mM and promote an inhibition of cell cycle progression induced by IL-2 (9). On the other hand, n-6 FAs have proinflammatory properties by increasing intercellular adhesion molecule-1 expression (13), natural killer cell activity (14), and IgE production (15).…”

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“…On the other hand, n-6 FAs have proinflammatory properties by increasing intercellular adhesion molecule-1 expression (13), natural killer cell activity (14), and IgE production (15). Linoleic acid (LA; C18:2 n-6) promotes an increase of lymphocyte proliferation at low concentration (25 mM) and increases the stimulatory effect of IL-2 on lymphocyte proliferation (9).…”

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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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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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“…Among these, free fatty acids were the most abundant class of lipids identified in our samples and they proved capable of mediating the enhanced T-cell proliferation when added individually. Although some scarce reports exist with contrasting results regarding the modulatory effect of fatty acids on T-cell proliferation [15][16][17] Eur. J. Immunol.…”

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confidence: 99%

Adipocyte‐derived lipids modulate CD4⁺ T‐cell function

et al. 2013

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Adipose tissue contains several immune cells whose number and phenotype vary depending on the adiposity. In the present study, we show that IFN-γ + CD4 + T cells are enriched in human adipose tissue compared with in blood. To gain insight into the underlying mechanisms, we investigated the possibility that human adipocytes modulate CD4 + T-cell cytokine production and proliferation and show that CD4 + T cells produced increased levels of IFN-γ when activated in the presence of adipocytes. This effect was mediated by soluble mediators, as shown in transwell and adipocyte-conditioned medium (ACM) transfer experiments. Additionally, ACM induced increased proliferation of CD4 + T cells upon activation. Intriguingly, the proliferation-enhancing effect resided mainly in the lipid fraction of ACM, as shown upon separation of the protein and lipid fraction. Further separation of these lipids based on polarity revealed that the modulatory effect is confined to fractions containing free fatty acids. All identified fatty acids were able to individually enhance T-cell proliferation. These data indicate that adipocytes can modulate CD4 + T-cell function through the release of lipids. Remarkably, free fatty acids were the most prominent modulators of T-cell proliferation, possibly leading to an accumulation of these cells in adipose tissue. Keywords: Adipocytes r CD4 + T cells r Lipids r ObesityAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAdipose tissue is composed of adipocytes, which are primarily involved in lipid storage and release, and the stromal vascular fraction (SVF). The composition of the SVF varies, depending on the localization of the adipose tissue and the degree of adiposity of the individual, but it typically contains a large variety Correspondence: Dr. Andreea Ioan-Facsinay e-mail: A.Ioan@lumc.nl of cells, including progenitor cells, fibroblasts, endothelial cells, nerve cells, and immune cells. Among the immune cells described in adipose tissue, macrophages and T cells are the most abundant, but other cells, like NK cells, mast cells, and B cells have also been described (reviewed in [1]). While the precise role of these cells in the adipose tissue is largely unknown, there is increasing evidence that cross-talk between immune cells and adipocytes exists and that the immune cells can influence the metabolic functions of the resident adipocytes (reviewed in [1] [2,3], or local differentiation/proliferation of resident T cells [5] under the influence of the adipose tissue environment could constitute underlying mechanisms for changes in the adipose tissue CD4 + T-cell population in obesity.Adipose tissue T cells have been previously shown to be present in the vicinity of adipocytes [3]. Moreover, some adipocytederived soluble mediators, such as leptin [10, have been shown to modulate differentiation or cytokine production by CD4 + T cells. However, adipocytes can release a large number of soluble mediators with different biologica...

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Effect of oleic and linoleic acids on the inflammatory phase of wound healing in rats

Pereira

Hatanaka

Martins

et al. 2007

Cell Biochemistry & Function

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Inflammation is a crucial step for the wound healing process. The effect of linoleic and oleic acids on the inflammatory response of the skin during the healing process and on the release of pro-inflammatory cytokines by rat neutrophils in vitro was investigated. A wound in the dorsal surface of adult rats was performed and fatty acids were then topically administered. Both oleic and linoleic acids increased the wound healing tissue mass. The total protein and DNA contents of the wounds were increased by the treatment with linoleic acid. The treatments with oleic and linoleic acids did not affect vascular permeability. However, the number of neutrophils in the wounded area and air pouches was increased and the thickness of the necrotic cell layer edge around the wound was decreased. A dose-dependent increase in vascular endothelial growth factor-alpha (VEGF-alpha) and interleukin-1beta (IL-1beta) by neutrophils incubated in the presence of oleic and linoleic acid was observed. Oleic acid was able to stimulate also the production of cytokine-induced neutrophil chemoattractant in inflammation 2 alpha/beta (CINC-2alpha/beta). This pro-inflammatory effect of oleic and linoleic acids may speed up the wound healing process.

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Regulation of human lymphocyte proliferation by fatty acids

Cited by 50 publications

References 57 publications

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

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

Adipocyte‐derived lipids modulate CD4⁺ T‐cell function

Effect of oleic and linoleic acids on the inflammatory phase of wound healing in rats

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Regulation of human lymphocyte proliferation by fatty acids

Cited by 50 publications

References 57 publications

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

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

Adipocyte‐derived lipids modulate CD4+ T‐cell function

Effect of oleic and linoleic acids on the inflammatory phase of wound healing in rats

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Adipocyte‐derived lipids modulate CD4⁺ T‐cell function