Immunomodulation of microglia by docosahexaenoic acid and eicosapentaenoic acid

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 15, Issue 2, 2012, Pages 134-143

  Hjorth, Erik ^a   Freund Levi, Yvonne ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

3 fatty acids; inflammation; microglia; phagocytosis; resolution

Indexed keywords

CD40 ANTIGEN; CD86 ANTIGEN; DOCOSAHEXAENOIC ACID; GAMMA INTERFERON; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 12; INTERLEUKIN 13; INTERLEUKIN 1BETA; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 8; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; OMEGA 3 FATTY ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; VOLTAGE GATED POTASSIUM CHANNEL;

ANTIINFLAMMATORY ACTIVITY; ASTROCYTE; CELL MEMBRANE; CENTRAL NERVOUS SYSTEM; HUMAN; IMMUNOMODULATION; INFLAMMATION; ION CURRENT; METABOLITE; MICROGLIA; NEUROMODULATION; NONHUMAN; PHAGOCYTOSIS; REVIEW;

ANIMALS; ANTI-INFLAMMATORY AGENTS; CENTRAL NERVOUS SYSTEM; DOCOSAHEXAENOIC ACIDS; EICOSAPENTAENOIC ACID; HUMANS; IMMUNOMODULATION; INFLAMMATION; MICROGLIA; MODELS, ANIMAL; PHAGOCYTOSIS;

EID: 84857059754     PISSN: 13631950     EISSN: 14736519     Source Type: Journal    
DOI: 10.1097/MCO.0b013e32835017cc     Document Type: Review

References (121)

1. Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and omega-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 2003; 60:940-946. (Pubitemid 36858352)
2. Bousquet M, Saint-Pierre M, Julien C, et al. Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson's disease. FASEB J 2008; 22:1213-1225. (Pubitemid 351519975)
3. Nordvik I, Myhr KM, Nyland H, et al. Effect of dietary advice and omega-3 supplementation in newly diagnosed MS patients. Acta Neurol Scand 2000; 102:143-149. (Pubitemid 30645133)
4. Arvindakshan M, Ghate M, Ranjekar PK, et al. Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Schizophr Res 2003; 62:195-204. (Pubitemid 36773928)
5. Eikelenboom P, Rozemuller JM, Kraal G, et al. Cerebral amyloid plaques in Alzheimer's disease but not in scrapie-Affected mice are closely associated with a local inflammatory process. Virchows Arch B Cell Pathol 1991; 60:329-336.
6. Bauer J, Strauss S, Schreiter-Gasser U, et al. Interleukin-6 and a-2-macroglobulin indicate an acute-phase state in Alzheimer's disease cortices. FEBS Lett 1991; 285:111-114.
7. Griffin WS, Stanley LC, Ling C, et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci 1989; 86:7611-7615. (Pubitemid 19254506)
8. Zaheer S, Thangavel R, Sahu S, et al. Augmented expression of glia maturation factor in Alzheimer's disease. Neuroscience 2011; 194:227-233.
9. Khandelwal P, Herman A, Moussa C. Inflammation in the early stages of neurodegenerative pathology. J Neuroimmunol 2011; 238:1-11.
10. Brightbill HD, Libraty DH, Krutzik SR, et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 1999; 285:732-736.
11. Pearl-Yafe M, Fabian I, Halperin D, et al. Interferon-g and bacterial lipopolysaccharide act synergistically on human neutrophils enhancing interleukin-8, interleukin-1b, tumor necrosis factor-A, and interleukin-12 p70 secretion and phagocytosis via upregulation of toll-like receptor 4. Shock 2007; 27:226-231.
12. Hauss-Wegrzyniak B, Lynch MA, Vraniak PD, et al. Chronic brain inflammation results in cell loss in the entorhinal cortex and impaired LTP in perforant path-granule cell synapses. Exp Neurol 2002; 176:336-341. (Pubitemid 35193350)
13. Stence N, Waite M, Dailey ME. Dynamics of microglial activation: A confocal time-lapse analysis in hippocampal slices. Glia 2001; 33:256-266. (Pubitemid 32219134)
14. Dalpke AH, Schafer MK, Frey M, et al. Immunostimulatory CpG-DNA activates murine microglia. J Immunol 2002; 168:4854-4863. (Pubitemid 34495946)
15. Olson JK, Miller SD. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol 2004; 173:3916-3924. (Pubitemid 39280755)
16. Alliot F, Godin I, Pessac B. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res 1999; 117:145-152. (Pubitemid 29531505)
17. Ginhoux F, Greter M, Leboeuf M, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010; 330:841-845. This study very elegantly answers the question of microglial origin which have been controversial for a long time
18. Abdel-Haq N, Hao HN, Lyman WD. Cytokine regulation of CD40 expression in fetal human astrocyte cultures. J Neuroimmunol 1999; 101:7-14. (Pubitemid 29505168)
19. D'Aversa TG, Eugenin EA, Berman JW. CD40-CD40 ligand interactions in human microglia induce CXCL8 (interleukin-8) secretion by a mechanism dependent on activation of ERK1/2 and nuclear translocation of nuclear factor-kappaB (NFkB) and activator protein-1 (AP-1). J Neurosci Res 2008; 86:630-639. (Pubitemid 351204476)
20. Chen K, Huang J, Gong W, et al. CD40/CD40L dyad in the inflammatory and immune responses in the central nervous system. Cell Mol Immunol 2006; 3:163-169.
21. Suzumura A, Sawada M, Itoh Y, et al. Interleukin-4 induces proliferation and activation of microglia but suppresses their induction of class II major histocompatibility complex antigen expression. J Neuroimmunol 1994; 53:209-218. (Pubitemid 24272012)
22. Chao CC, Hu S, Molitor TW, et al. Activated microglia mediate neuronal cell injury via a nitric oxide mechanism. J Immunol 1992; 149:2736-2741.
23. Choi JS, Jung SW, Ju JC, et al. Cytokine production regulation in human astrocytes by a herbal combination (Yuldahansotang). Immunopharmacol Immunotoxicol 2002; 24:55-67.
24. Ponomarev ED, Maresz K, Tan Y, et al. CNS-derived interleukin-4 is essential for the regulation of autoimmune inflammation and induces a state of alternative activation in microglial cells. J Neurosci 2007; 27:10714-10721. (Pubitemid 47535871)
25. Clarke RM, Lyons A, O'Connell F, et al. A pivotal role for interleukin-4 in atorvastatin-Associated neuroprotection in rat brain. J Biol Chem 2008; 283:1808-1817.
26. Vereker E, O'Donnell E, Lynch MA. The inhibitory effect of interleukin-1b on long-term potentiation is coupled with increased activity of stress-Activated protein kinases. J Neurosci 2000; 20:6811-6819.
27. Vereker E, O'Donnell E, Lynch A, et al. Evidence that interleukin-1b and reactive oxygen species production play a pivotal role in stress-induced impairment of LTP in the rat dentate gyrus. Eur J Neurosci 2001; 14:1809-1819. (Pubitemid 35463699)
28. Curran B, O'Connor JJ. The pro-inflammatory cytokine interleukin-18 impairs long-term potentiation and NMDA receptor-mediated transmission in the rat hippocampus in vitro. Neuroscience 2001; 108:83-90. (Pubitemid 33152983)
29. Hjorth E, Frenkel D, Weiner H, et al. Effects of immunomodulatory substances on phagocytosis of Ab1-42 by human microglia. Int J Alzheimer's Dis 2010; pii: 798424. PMID: 20798889.
30. Yagnik DR, Evans BJ, Florey O, et al. Macrophage release of transforming growth factor-b1 during resolution of monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum 2004; 50:2273-2280. (Pubitemid 38924406)
31. Prüss H, Kopp M, Brommer B, et al. Non-resolving aspects of acute inflammation after spinal cord injury (SCI): Indices and resolution plateau. Brain Pathol 2011; 31:652-660.
32. Kondo T, Ishida Y. Molecular pathology of wound healing. Forensic Sci Int 2010; 203:93-98.
33. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev 2003; 83:835-870. (Pubitemid 36828927)
34. Serhan CN, Hamberg M, Samuelsson B. Lipoxins: Novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc Natl Acad Sci USA 1984; 81:5335-5339. (Pubitemid 14048742)
35. Serhan CN, Yang R, Martinod K, et al. Maresins: Novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 2009; 206:15-23.
36. Mukherjee PK, Marcheselli VL, Serhan CN, et al. Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci USA 2004; 101:8491-8496. (Pubitemid 38736602)
37. Serhan CN, Hong S, Gronert K, et al. Resolvins: A family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 2002; 196:1025-1037. (Pubitemid 35231761)
38. Wang Y, Wu Y, Li L, et al. Aspirin-triggered lipoxin A4 attenuates LPSinduced pro-inflammatory responses by inhibiting activation of NF-kB and MAPKs in BV-2 microglial cells. J Neuroinflammation 2011; 8:95.
39. Li N, He J, Schwartz CE, et al. Resolvin E1 improves tear production and decreases inflammation in a dry eye mouse model. J Ocul Pharmacol Ther 2010; 26:431-439.
40. Lund T, Mangsbo SM, Scholz H, et al. Resolvin E1 reduces proinflammatory markers in human pancreatic islets in vitro. Exp Clin Endocrinol Diabetes 2010; 118:237-244.
41. HongS,Gronert K,DevchandPR, et al. Noveldocosatrienes and17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in antiinflammation. J Biol Chem 2003; 278:14677-14687. (Pubitemid 36799790)
42. Haslett C, Savill JS, Whyte MK, et al. Granulocyte apoptosis and the control of inflammation. Philos Trans R Soc Lond B Biol Sci 1994; 345:327-333.
43. Stern M, Savill J, Haslett C. Human monocyte-derived macrophage phagocytosis of senescent eosinophils undergoing apoptosis. Mediation by avb3/CD36/thrombospondin recognition mechanism and lack of phlogistic response. Am J Pathol 1996; 149:911-921. (Pubitemid 26334175)
44. Krishnamoorthy S, Recchiuti A, Chiang N, et al. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci USA 2010; 107:1660-1665. In this study, the authors for the first time describe receptors for PRFs derived from DHA and EPA, thus laying the ground for pharmaceutical investigation on the molecular mechanisms of induction of resolution by PRFs.
45. Freund-Levi Y, Hjorth E, Lindberg C, et al. Effects of omega-3 fatty acids on inflammatory markers in cerebrospinal fluid and plasma in Alzheimer's disease: The OmegAD study. Dementia and Geriatric Cognitive Disorders 2009; 27:481-490.
46. Lu DY, Tsao YY, Leung YM, et al. Docosahexaenoic acid suppresses neuroinflammatory responses and induces heme oxygenase-1 expression in BV-2 microglia: Implications of antidepressant effects for omega-3 fatty acids. Neuropsychopharmacology 2010; 35:2238-2248.
47. Moon DO, Kim KC, Jin CY, et al. Inhibitory effects of eicosapentaenoic acid on lipopolysaccharide-induced activation in BV2 microglia. Int Immunopharmacol 2007; 7:222-229.
48. Kawashima A, Harada T, Imada K, et al. Eicosapentaenoic acid inhibits interleukin-6 production in interleukin-1b-stimulated C6 glioma cells through peroxisome proliferator-Activated receptor-g. Prostaglandins Leukot Essent Fatty Acids 2008; 79:59-65.
49. Draper E, Reynolds C, Canavan M, et al. Omega-3 fatty acids attenuate dendritic cell function via NF-kB independent of PPAR-g. J Nutr Biochem 2011; 22:784-790.
50. Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: A randomized double-blind trial. Arch Neurol 2006; 63:1402-1408. (Pubitemid 44547551)
51. Vedin I, Cederholm T, Freund Levi Y, et al. Effects of docosahexaenoic acidrich omega-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: The OmegAD study. Am J Clin Nutr 2008; 87:1616-1622. (Pubitemid 351872622)
52. Ebert S, Weigelt K, Walczak Y, et al. Docosahexaenoic acid attenuates microglial activation and delays early retinal degeneration. J Neurochem 2009; 110:1863-1875.
53. Lalancette-Hébert M, Julien C, Cordeau P, et al. Accumulation of dietary docosahexaenoic acid in the brain attenuates acute immune response and development of postischemic neuronal damage. Stroke 2011; 42:2903-2909.
54. Wang H, Khor TO, Saw CL, et al. Role of Nrf2 in suppressing LPS-induced inflammation in mouse peritoneal macrophages by polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid. Mol Pharmaceut 2010; 7:2185-2193.
55. Hardy JA, Higgins GA. Alzheimer's disease: Amyloid cascade hypothesis. Science 1992; 256:184-185.
56. Halvorsen DS, Hansen JB, Grimsgaard S, et al. The effect of highly purified eicosapentaenoic and docosahexaenoic acids on monocyte phagocytosis in man. Lipids 1997; 32:935-942. (Pubitemid 27398486)
57. Gorjao R, Verlengia R, Lima TM, et al. Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function. Clin Nutr 2006; 25:923-938. (Pubitemid 44752719)
58. Kew S, Gibbons ES, Thies F, et al. The effect of feeding structured triacylglycerols enriched in eicosapentaenoic or docosahexaenoic acids on murine splenocyte fatty acid composition and leucocyte phagocytosis. Br J Nutr 2003; 90:1071-1080. (Pubitemid 37548039)
59. Pisani LF, Lecchi C, Invernizzi G, et al. In vitro modulatory effect of omega-3 polyunsaturated fatty acid (EPA and DHA) on phagocytosis and ROS production of goat neutrophils. Vet Immunol Immunopathol 2009; 131:79-85.
60. Sipka S, Dey I, Buda C, et al. The mechanism of inhibitory effect of eicosapentaenoic acid on phagocytic activity and chemotaxis of human neutrophil granulocytes. Clin Immunol Immunopathol 1996; 79:224-228. (Pubitemid 26179876)
61. Hasturk H, Kantarci A, Goguet-Surmenian E, et al. Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol 2007; 179:7021-7029.
62. Seki H, Fukunaga K, Arita M, et al. The anti-inflammatory and proresolving mediator resolvin E1 protects mice from bacterial pneumonia and acute lung injury. J Immunol 2010; 184:836-843.
63. Haworth O, Cernadas M, Yang R, et al. Resolvin E1 regulates interleukin 23, interferon-g and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat Immunol 2008; 9:873-879.
64. Zhao Y, Calon F, Julien C, et al. Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase-And PPAR-g-mediated mechanisms in Alzheimer's disease models. PLoS One 2011; 6:e15816. This study describes a common neuroprotective pathway for DHA and a proresolving derivate, which has implications for future therapies for neurodegenerative disorders such as Alzheimer's disease.
65. Schwab JM, Chiang N, Arita M, et al. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 2007; 447:869-874. (Pubitemid 46920139)
66. Cash JL, Christian AR, Greaves DR. Chemerin peptides promote phagocytosis in a ChemR23-And Syk-dependent manner. J Immunol 2010; 184:5315-5324.
67. Profita M, Sala A, Siena L, et al. Leukotriene B4 production in human mononuclear phagocytes is modulated by interleukin-4-induced 15-lipoxygenase. J Pharmacol Exp Ther 2002; 300:868-875. (Pubitemid 34164990)
68. Brown CD, Kilty I, Yeadon M, et al. Regulation of 15-lipoxygenase isozymes and mucin secretion by cytokines in cultured normal human bronchial epithelial cells. Inflamm Res 2001; 50:321-326. (Pubitemid 32607780)
69. Nassar GM, Montero A, Fukunaga M, et al. Contrasting effects of proinflammatory and T-helper lymphocyte subset-2 cytokines on the 5-lipoxygenase pathway in monocytes. Kidney Int 1997; 51:1520-1528. (Pubitemid 27239907)
70. Dixon RA, Diehl RE, Opas E, et al. Requirement of a 5- lipoxygenaseactivating protein for leukotriene synthesis. Nature 1990; 343:282-284.
71. Pouliot M, McDonald PP, Borgeat P, et al. Granulocyte/macrophage colonystimulating factor stimulates the expression of the 5-lipoxygenase- Activating protein (FLAP) in human neutrophils. J Exp Med 1994; 179:1225-1232. (Pubitemid 24091781)
72. Bongrazio M, Roscher A, Ludwig P, et al. Loss of cytosolic 15-lipoxygenase activity in A23187-stimulated human leukocytes: Involvement of a translocation process? Eicosanoids 1992; 5:191-195. (Pubitemid 23041954)
73. Watson A, Doherty FJ. Calcium promotes membrane association of reticulocyte 15-lipoxygenase. Biochem J 1994; 298:377-383. (Pubitemid 24072480)
74. Ariel A, Li PL, Wang W, et al. The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering. J Biol Chem 2005; 280:43079-43086. (Pubitemid 43049274)
75. Levy BD, Clish CB, Schmidt B, et al. Lipid mediator class switching during acute inflammation: Signals in resolution. Nat Immunol 2001; 2:612-619. (Pubitemid 32677628)
76. Luo M, Jones SM, Phare SM, et al. Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5-lipoxygenase on serine 523. J Biol Chem 2004; 279:41512-41520. (Pubitemid 39313592)
77. Ye Y, Lin Y, Perez-Polo JR, et al. Phosphorylation of 5-lipoxygenase at ser523 by protein kinase A determines whether pioglitazone and atorvastatin induce proinflammatory leukotriene B4 or anti-inflammatory 15-epi-lipoxin a4 production. J Immunol 2008; 181:3515-3523.
78. Khanna S, Roy S, Slivka A, et al. Neuroprotective properties of the natural vitamin E alpha-tocotrienol. Stroke 2005; 36:2258-2264. (Pubitemid 41429256)
79. Forslin Aronsson A, Spulber S, Oprica M, et al. Alpha-MSH rescues neurons from excitotoxic cell death. J Mol Neurosci 2007; 33:239-251. (Pubitemid 350242533)
80. Forslin Aronsson S, Spulber S, Popescu LM, et al. alpha-Melanocyte- stimulating hormone is neuroprotective in rat global cerebral ischemia. Neuropeptides 2006; 40:65-75. (Pubitemid 43255414)
81. Zhang Z, Yao K, Ma J, et al. Anti-inflammatory effect of the alpha-melanocyte stimulating hormone in animal eyes undergoing extracapsular lens extraction. Mol Biol 2011; 45:272-281.
82. Chu LS, Fang SH, Zhou Y, et al. Minocycline inhibits 5-lipoxygenase expression and accelerates functional recovery in chronic phase of focal cerebral ischemia in rats. Life Sci 2010; 86:170-177.
83. Chu LS, Fang SH, Zhou Y, et al. Minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal cerebral ischemia in rats. Acta Pharmacol Sin 2007; 28:763-772. (Pubitemid 46817443)
84. Li H, Ruan XZ, Powis SH, et al. EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: Evidence for a PPAR-g-dependent mechanism. Kidney Int 2005; 67:867-874. (Pubitemid 41623311)
85. Ricote M, Li AC, Willson TM, et al. The peroxisome proliferator-Activated receptor-g is a negative regulator of macrophage activation. Nature 1998; 391:79-82. (Pubitemid 28079218)
86. Nguyen VT, Benveniste EN. Involvement of STAT-1 and ets family members in interferon-g induction of CD40 transcription in microglia/macrophages. J Biol Chem 2000; 275:23674-23684. (Pubitemid 30624652)
87. Manni A, Kleimberg J, Ackerman V, et al. Inducibility of RANTES mRNA by IL-1b in human bronchial epithelial cells is associated with increased NF-kB DNA binding activity. Biochem Biophys Res Commun 1996; 220:120-124. (Pubitemid 26106809)
88. Majai G, Sarang Z, Csomos K, et al. PPAR-g-dependent regulation of human macrophages in phagocytosis of apoptotic cells. Eur J Immunol 2007; 37:1343-1354. (Pubitemid 46925318)
89. Zhao X, Sun G, Zhang J, et al. Hematoma resolution as a target for intracerebral hemorrhage treatment: Role for peroxisome proliferatoractivated receptor-g in microglia/macrophages. Ann Neurol 2007; 61:352-362. (Pubitemid 46676735)
90. Pfeiffer A, Bottcher A, Orso E, et al. Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts. Eur J Immunol 2001; 31:3153-3164. (Pubitemid 33100507)
91. Hashimoto M, Hossain S, Yamasaki H, et al. Effects of eicosapentaenoic acid and docosahexaenoic acid on plasma membrane fluidity of aortic endothelial cells. Lipids 1999; 34:1297-1304. (Pubitemid 30044268)
92. Triantafilou M, Miyake K, Golenbock DT, et al. Mediators of innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation. J Cell Sci 2002; 115:2603-2611. (Pubitemid 34778077)
93. Wong SW, Kwon MJ, Choi AM, et al. Fatty acids modulate toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner. J Biol Chem 2009; 284:27384-27392.
94. Rockett BD, Franklin A, Harris M, et al. Membrane raft organization is more sensitive to disruption by omega-3 PUFA than nonraft organization in EL4 and B cells. J Nutr 2011; 141:1041-1048.
95. De Smedt-Peyrusse V, Sargueil F, Moranis A, et al. Docosahexaenoic acid prevents lipopolysaccharide-induced cytokine production in microglial cells by inhibiting lipopolysaccharide receptor presentation but not its membrane subdomain localization. J Neurochem 2008; 105:296-307. (Pubitemid 351490003)
96. Chen W, Jump DB, Esselman WJ, et al. Inhibition of cytokine signaling in human retinal endothelial cells through modification of caveolae/lipid rafts by docosahexaenoic acid. Invest Ophthalmol Vis Sci 2007; 48:18-26. (Pubitemid 47251381)
97. Hagi A, Nakayama M, Shinzaki W, et al. Effects of the omega-6:omega-3 fatty acid ratio of fat emulsions on the fatty acid composition in cell membranes and the anti-inflammatory action. JPEN J Parenter Enteral Nutr 2010; 34:263-270.
98. Villalonga N, David M, Bielanska J, et al. Immunomodulation of voltagedependent K+ channels in macrophages: Molecular and biophysical consequences. J Gen Physiol 2010; 135:135-147.
99. Pyo H, Chung S, Jou I, et al. Expression and function of outward K+ channels induced by lipopolysaccharide in microglia. Mol Cells 1997; 7:610-614. (Pubitemid 127477543)
100. Kaushal V, Koeberle PD, Wang Y, et al. The Ca2+-Activated K+ channel KCNN4/KCa3.1 contributes to microglia activation and nitric oxide-dependent neurodegeneration. J Neurosci 2007; 27:234-244. (Pubitemid 46089977)
101. McLarnon JG, Franciosi S, Wang X, et al. Acute actions of tumor necrosis factor-A on intracellular Ca2+ and K+ currents in human microglia. Neuroscience 2001; 104:1175-1184. (Pubitemid 32701976)
102. Vicente R, Escalada A, Coma M, et al. Differential voltage-dependent K+ channel responses during proliferation and activation in macrophages. J Biol Chem 2003; 21:46307-46320. (Pubitemid 37452201)
103. Jo HY, Kim SY, Lee S, et al. Kir3.1 channel is functionally involved in TLR4-mediated signaling. Biochem Biophys Res Commun 2011; 407:687-691.
104. Li GR, Sun HY, Zhang XH, et al. Omega-3 polyunsaturated fatty acids inhibit transient outward and ultra-rapid delayed rectifier K+currents and Na+curcurrent in human atrial myocytes. Cardiovasc Res 2009; 81:286-293.
105. Li HX, Wang RX, Li XR, et al. Increasing DHA and EPA concentrations prolong action potential durations and reduce transient outward potassium currents in rat ventricular myocytes. Lipids 2011; 46:163-170.
106. Seebungkert B, Lynch JW. Effects of polyunsaturated fatty acids on voltagegated K+ and Na+ channels in rat olfactory receptor neurons. Eur J Neurosci 2002; 16:2085-2094. (Pubitemid 35454253)
107. Poling JS, Vicini S, Rogawski MA, et al. Docosahexaenoic acid block of neuronal voltage-gated K+ channels: Subunit selective antagonism by zinc. Neuropharmacology 1996; 35:969-982. (Pubitemid 26377683)
108. Wu KT, Huang CT, Wei J, et al. Vasodilator action of docosahexaenoic acid (DHA) in human coronary arteries in vitro. Chin J Physiol 2007; 50:164-170.
109. Franciosi S, Choi HB, Kim SU, et al. Interferon-g acutely induces calcium influx in human microglia. J Neurosci Res 2002; 69:607-613. (Pubitemid 34966873)
110. Dolmetsch R, Lewis R, Goodnow C, et al. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 1997; 24:855-858. (Pubitemid 27181262)
111. Pepe S, Bogdanov K, Hallaq H, et al. Omega-3 polyunsaturated fatty acid modulates dihydropyridine effects on L-type Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes. Proc Natl Acad Sci USA 1994; 91:8832-8836. (Pubitemid 2148794)
112. Hirafuji M, Ebihara T, Kawahara F, et al. Effect of docosahexaenoic acid on intracellular calcium dynamics in vascular smooth muscle cells from normotensive and genetically hypertensive rats. Res Commun Mol Pathol Pharmacol 1998; 102:29-42. (Pubitemid 29058450)
113. Martens JR, O'Connell K, Tamkun M. Targeting of ion channels to membrane microdomains: Localization of KV channels to lipid rafts. Trends Pharmacol Sci 2004; 25:16-21. (Pubitemid 38076952)
114. Weaver AK, Olsen ML, McFerrin MB, et al. BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: A novel mechanism for coupling [Ca(2+)](i) to ion channel activation. J Biol Chem 2007; 282:31558-31568. (Pubitemid 350044881)
115. Shmygol A, Noble K, Wray S. Depletion of membrane cholesterol eliminates the Ca2+-Activated component of outward potassium current and decreases membrane capacitance in rat uterine myocytes. J Physiol 2007; 581:445-456. (Pubitemid 46831748)
116. An H, Yu Y, Zhang M, et al. Involvement of ERK, p38 and NF-kB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells. Immunology 2002; 106:38-45. (Pubitemid 34437875)
117. Wissel H, Schulz C, Koehne P, et al. Chlamydophila pneumoniae induces expression of toll-like receptor 4 and release of TNF-A and MIP-2 via an NF-kB pathway in rat type II pneumocytes. Respir Res 2005; 6:51.
118. Wall R, Ross RP, Fitzgerald GF, et al. Fatty acids from fish: The antiinflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 2010; 68:280-289.
119. Jicha GA, Markesbery WR. Omega-3 fatty acids: Potential role in the management of early Alzheimer's disease. Clin Interv Aging 2010; 5:45-61.
120. Cederholm T, Palmblad J. Are omega-3 fatty acids options for prevention and treatment of cognitive decline and dementia? Curr Opin Clin Nutr Metab Care 2010; 13:150-155.
121. Yurko-Mauro K, McCarthy D, Rom D, et al. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 2010; 6:456-464.