Comparative Effects of n-3, n-6 and n-9 Unsaturated Fatty Acid-Rich Diet Consumption on Lupus Nephritis, Autoantibody Production and CD4+ T Cell-Related Gene Responses in the Autoimmune NZBWF1 Mouse

作者: James J. Pestka , Laura L. Vines , Melissa A. Bates , Kaiyu He , Ingeborg Langohr

DOI: 10.1371/JOURNAL.PONE.0100255

关键词: ImmunologyGlomerulonephritisT cellBiologyAutoantibodyLupus nephritisPolyunsaturated fatty acidEndocrinologyAutoimmunityInternal medicineAutoimmune diseaseUnsaturated fatty acid

摘要: Mortality from systemic lupus erythematosus (SLE), a prototypical autoimmune disease, correlates with the onset and severity of kidney glomerulonephritis. There are both preclinical clinical evidence that SLE patients may benefit consumption n-3 polyunsaturated fatty acids (PUFA) found in fish oil, but mechanisms remain unclear. Here we employed NZBWF1 mouse model to compare effects dietary lipids on glomerulonephritis after consuming: 1) PUFA-rich diet containing docosahexaenoic acid-enriched oil (DFO), 2) n-6 Western-type corn (CRN) or 3) n-9 monounsaturated acid (MUFA)-rich Mediterranean-type high oleic safflower (HOS). Elevated plasma autoantibodies, proteinuria were evident mice fed either PUFA MUFA diets, however, all three endpoints markedly attenuated consumed until 34 wk age. A focused PCR array was used relate these findings expression 84 genes associated CD4+ T cell function spleen prior nephritis. suppression autoimmunity co-occur generalized downregulation cell-related and/or at 34. These inflammatory response, antigen presentation, activation, B activation/differentiation leukocyte recruitment. Quantitative RT-PCR representative affected confirmed reduced CD80, CTLA-4, IL-10, IL-18, CCL-5, CXCR3, IL-6, TNF-α osteopontin mRNAs spleens as compared diets. Remarkably, many identified this study currently under consideration biomarkers biotherapeutic targets for other diseases.

参考文章(114)
M. Zeher, S. Sipka, G. Szegedi, Boglarka Brugos, Z. Vincze, Serum and urinary cytokine levels of SLE patients. Die Pharmazie. ,vol. 67, pp. 411- 413 ,(2012) , 10.1691/PH.2012.1694
Allison Sang, Yiming Yin, Ying-Yi Zheng, Laurence Morel, Animal models of molecular pathology systemic lupus erythematosus. Progress in Molecular Biology and Translational Science. ,vol. 105, pp. 321- 370 ,(2012) , 10.1016/B978-0-12-394596-9.00010-X
Shozo Izui, T. B. Strom, A. Ferretti, V. E. Kelley, A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus in MRL-lpr mice. Journal of Immunology. ,vol. 134, pp. 1914- 1919 ,(1985)
Anja E. Hauser, Gudrun F. Debes, Sergio Arce, Giuliana Cassese, Alf Hamann, Andreas Radbruch, Rudolf A. Manz, Chemotactic Responsiveness Toward Ligands for CXCR3 and CXCR4 Is Regulated on Plasma Blasts During the Time Course of a Memory Immune Response Journal of Immunology. ,vol. 169, pp. 1277- 1282 ,(2002) , 10.4049/JIMMUNOL.169.3.1277
T Ozeri-Chen, R J Deans, D J Wallace, J R Klinenberg, J Prehn, M Linker-Israeli, Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis. Journal of Immunology. ,vol. 147, pp. 117- 123 ,(1991)
Banafsheh Mirnikjoo, Sarah E. Brown, H. Florence Seung Kim, Lauren B. Marangell, J. David Sweatt, Edwin J. Weeber, Protein Kinase Inhibition by ω-3 Fatty Acids * Journal of Biological Chemistry. ,vol. 276, pp. 10888- 10896 ,(2001) , 10.1074/JBC.M008150200
Vicki E. Kelley, Mary A. Yui, Daniel C. Brennan, Rudolf P. Wuthrich, Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury. Journal of Immunology. ,vol. 143, pp. 3470- 3475 ,(1989)
Oliver M. Steinmetz, Jan-Eric Turner, Hans-Joachim Paust, Matthias Lindner, Anett Peters, Kirstin Heiss, Joachim Velden, Helmut Hopfer, Susanne Fehr, Thorsten Krieger, Catherine Meyer-Schwesinger, Tobias N. Meyer, Udo Helmchen, Hans-Willi Mittrücker, Rolf A. K. Stahl, Ulf Panzer, CXCR3 Mediates Renal Th1 and Th17 Immune Response in Murine Lupus Nephritis Journal of Immunology. ,vol. 183, pp. 4693- 4704 ,(2009) , 10.4049/JIMMUNOL.0802626
R Patarca, H Cantor, M V Iregui, M A Lampe, Polyclonal B cell activation by the Eta-1 cytokine and the development of systemic autoimmune disease. Journal of Immunology. ,vol. 147, pp. 2902- 2906 ,(1991)