n-3 Polyunsaturated fatty acids exert immunomodulatory effects on lymphocytes by targeting plasma membrane molecular organization.
Fish oil, enriched in bioactive n-3 polyunsaturated fatty acids (PUFA), has therapeutic value for the treatment of inflammation-associated disorders. The effects of n-3 PUFAs are pleiotropic and complex; hence, an understanding of their cellular targets and molecular mechanisms of action remains incomplete. Here we focus on recent data indicating n-3 PUFAs exert immunosuppressive effects on the function of effector and regulatory CD4(+) T cells. In addition, we also present emerging evidence that n-3 PUFAs have immunomodulatory effects on B cells. We then focus on one multifaceted mechanism of n-3 PUFAs, which is the alteration of the biophysical and biochemical organization of the plasma membrane. This mechanism is central for downstream signaling, eicosanoid production, transcriptional regulation and cytokine secretion. We highlight recent work demonstrating n-3 PUFA acyl chains in the plasma membrane target the lateral organization of membrane signaling assemblies (i.e. lipid rafts or signaling networks) and de novo phospholipid biosynthesis. We conclude by proposing new functional and mechanistic questions in this area of research that will aid in the development of fish oil as adjuvant therapy for treating unresolved chronic inflammation.
Department of Biochemistry & Molecular Biology and East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA. shaikhsa@ecu.edu
Saame Raza
SR
Shaikh
Christopher A
CA
Jolly
Robert S
RS
Chapkin
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D007155:Immunologic Factors