Oral administration of unsaturated fatty acids: effects on human peripheral blood T lymphocyte proliferation

Rossetti, Ronald G.; Seiler, Christina M.; DeLuca, Pamela; Laposata, Michael; Zurier, Robert B.

doi:10.1002/jlb.62.4.438

Cited by 63 publications

(31 citation statements)

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“…Both omega-6 and omega-3 PUFAs are competitive inhibitors of arachidonic acid, whose metabolites are involved in the inflammation process (Callegari and Zurier 1991;Gil 2002), and were demonstrated to decrease T cell proliferation (Rossetti et al 1997). On the other hand, molecules derived from PUFAs could have positive effects on the treatment of MS: Lipoxins might reduce inflammation by decreasing neutrophil activity (Yacoubian and Serhan 2007), while resolvins and protectins, derived from omega-3 PUFAs, seem to control inflammation in the nervous system (Serhan et al 2002).…”

Section: Demyelination/remyelination and Nutrientsmentioning

confidence: 99%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

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Demyelination is a pathological process characterized by the loss of myelin around axons. In the central nervous system, oligodendroglial damage and demyelination are common pathological features characterizing white matter and neurodegenerative disorders. Remyelination is a regenerative process by which myelin sheaths are restored to demyelinated axons, resolving functional deficits. This process is often deficient in demyelinating diseases such as multiple sclerosis (MS), and the reasons for the failure of repair mechanisms remain unclear. The characterization of these mechanisms and the factors involved in the proliferation, recruitment, and differentiation of oligodendroglial progenitor cells is key in designing strategies to improve remyelination in demyelinating disorders. First, a very dynamic combination of different molecules such as growth factors, cytokines, chemokines, and different signaling pathways is tightly regulated during the remyelination process. Second, factors unrelated to this pathology, i.e., age and genetic background, may impact disease progression either positively or negatively, and in particular, age-related remyelination failure has been proven to involve oligodendroglial cells aging and their intrinsic capacities among other factors. Third, nutrients may either help or hinder disease progression. Experimental evidence supports the anti-inflammatory role of omega-6 and omega-3 polyunsaturated fatty acids through the competitive inhibition of arachidonic acid, whose metabolites participate in inflammation, and the reduction in T cell proliferation. In turn, vitamin D intake and synthesis have been associated with lower MS incidence levels, while vitamin D-gene interactions might be involved in the pathogenesis of MS. Finally, dietary polyphenols have been reported to mitigate demyelination by modulating the immune response.

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Section: Demyelination/remyelination and Nutrientsmentioning

confidence: 99%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

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“…Administration of DHA (an n-3 derivative) improved cardiac response to stress [103], decreased the level of aggression [48,107], decreased stress responses [47,104,107,108], and decreased the level of prostaglandin E2 [31,103].…”

Section: Efa and Stressmentioning

confidence: 99%

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Yehuda¹,

Rabinovitz²,

Carasso³

et al. 2002

Neurobiology of Aging

353

200

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In addition to a gradual loss of neurons in various brain regions, major biochemical changes in the brain affect the neuronal membrane that is the "site of action" for many essential functions including long-term potentiation (LTP), learning and memory, sleep, pain threshold, and thermoregulation. Normal physiological functioning includes the transmission of axonal information, regulation of membrane-bound enzymes, control of ionic channels and various receptors. All are highly dependent on membrane fluidity, where rigidity is increased during aging. The significantly higher level of cholesterol in aging neuronal membrane, the slow rate of cholesterol turnover, and the decreased level of total polyunsaturated fatty acids (PUFA) may result from poor passage rate via the blood-brain barrier, or from a decreased rate of incorporation into the membrane, or a decrease in the activities of delta-6 and delta-9 desaturase enzymes. The added oxidative stress, which leads to an increase of free radicals leading to a decrease in membrane fluidity, may respond to a restricted diet, and thereby overcome the damaging effects of the free radicals. A central focus of this review is that a specific ratio of n-3/n-6 PUFA can restore many of these age-related effects.

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“…The molecular mechanism by which PUFAs inhibit T cell signal transduction has remained largely unknown. Because PUFA treatment changes the lipid composition of lymphocyte membranes (9) and functionally important membrane lipid rafts (10), alterations of rafts have been suggested as underlying the PUFA-mediated inhibition of T cell signaling (11).…”

Section: Polyunsaturated Fatty Acids (Pufas)mentioning

confidence: 99%

LAT Displacement from Lipid Rafts as a Molecular Mechanism for the Inhibition of T Cell Signaling by Polyunsaturated Fatty Acids

Zeyda¹,

Staffler²,

Hořejšı́³

et al. 2002

Journal of Biological Chemistry

152

105

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Polyunsaturated fatty acids (PUFAs) suppress immune responses and inhibit T cell activation through largely unknown mechanisms. The displacement of signaling proteins from membrane lipid rafts has recently been suggested as underlying PUFA-mediated T cell inhibition. We show here that PUFA treatment specifically interferes with T cell signal transduction by blocking tyrosine phosphorylation of LAT (linker for activation of T cells) and phospholipase C␥1. A significant fraction of LAT was displaced from rafts by PUFA treatment along with other signaling proteins. However, retaining LAT alone in lipid rafts effectively restored phospholipase C␥1/calcium signaling in PUFA-treated T cells. These data reveal LAT displacement from lipid rafts as a molecular mechanism by which PUFAs inhibit T cell signaling and underline the predominant importance of LAT localization in rafts for efficient T cell activation. Polyunsaturated fatty acids (PUFAs)1 suppress immune responses (1) and are clinically applied as adjuvant immunosuppressive agents in the treatment of inflammatory disorders (e.g. rheumatoid arthritis and inflammatory bowel disease) (2, 3) and following organ transplantation (4). PUFAs of the n-3 series have been shown to be particularly effective and are known to interfere with proinflammatory eicosanoid (prostaglandin/leukotriene) synthesis (1). However, PUFA-mediated inhibition of T lymphocyte activation and function has repeatedly been shown to be independent of eicosanoid synthesis (5-8). The molecular mechanism by which PUFAs inhibit T cell signal transduction has remained largely unknown. Because PUFA treatment changes the lipid composition of lymphocyte membranes (9) and functionally important membrane lipid rafts (10), alterations of rafts have been suggested as underlying the PUFA-mediated inhibition of T cell signaling (11).Membrane lipid rafts or microdomains are specialized regions within the plane of the plasma membrane and have been proposed as playing an essential role in T cell signal transduction (12-16). Lipid rafts are characterized by a high concentration of cholesterol and sphingolipids such as sphingomyelin and glycolipids, and their polar lipids contain predominantly saturated fatty acyl residues (17, 18). Such lipids spontaneously form liquid-ordered membrane regions that are insoluble in non-ionic detergents, facilitating raft isolation as detergentresistant membrane domains (18,19). Cytoplasmic and transmembrane proteins are targeted to lipid rafts mostly by acylation with saturated fatty acyl moieties (palmitoyl and myristoyl) which link these proteins to the cytoplasmic lipid leaflet of microdomains (20). Several proteins involved in T cell signaling such as Src family protein-tyrosine kinases (PTKs) and LAT (linker for activation of T cells) are concentrated in rafts because of post-translational palmitoylation, emphasizing the role of lipid rafts in T cell signaling (14, 21).The activation of T cells requires stimulation of the T cell antigen receptor (TCR)/CD3 complex. Triggering CD3...

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Oral administration of unsaturated fatty acids: effects on human peripheral blood T lymphocyte proliferation

Cited by 63 publications

References 0 publications

Nutritional factors and aging in demyelinating diseases

Nutritional factors and aging in demyelinating diseases

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

LAT Displacement from Lipid Rafts as a Molecular Mechanism for the Inhibition of T Cell Signaling by Polyunsaturated Fatty Acids

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