Regulatory activity of polyunsaturated fatty acids in T-cell signaling.
n-3 Polyunsaturated fatty acids (PUFA) are considered to be authentic immunosuppressors and appear to exert beneficial effects with respect to certain immune-mediated diseases. In addition to promoting T-helper 1 (Th1) cell to T-helper 2 (Th2) cell effector T-cell differentiation, n-3 PUFA may also exert anti-inflammatory actions by inducing apoptosis in Th1 cells. With respect to mechanisms of action, effects range from the modulation of membrane receptors to gene transcription via perturbation of a number of second messenger cascades. In this review, the putative targets of anti-inflammatory n-3 PUFA, activated during early and late events of T-cell activation will be discussed. Studies have demonstrated that these fatty acids alter plasma membrane micro-organization (lipid rafts) at the immunological synapse, the site where T-cells and antigen-presenting cells (APC) form a physical contact for antigen initiated T-cell signaling. In addition, the production of diacylglycerol and the activation of different isoforms of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), calcium signaling, and nuclear translocation/activation of transcriptional factors, can be modulated by n-3 PUFA. Advantages and limitations of diverse methodologies to study the membrane lipid raft hypothesis, as well as apparent contradictions regarding the effect of n-3 PUFA on lipid rafts will be critically presented.
Kim
Wooki
W
Program in Integrative Nutrition and Complex Diseases, Center for Environmental and Rural Health, Texas A&M University, USA.
Khan
Naim A
NA
McMurray
David N
DN
Prior
Ian A
IA
Wang
Naisyin
N
Chapkin
Robert S
RS
D017209:Apoptosis; D020013:Calcium Signaling; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases