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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.
PLoS One 2014; 9(6):e100255Plos

Abstract

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

Authors+Show Affiliations

Department of Food Science and Human Nutrition, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America; Center for Integrative Toxicology, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America; Department of Microbiology and Molecular Genetics, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America.Department of Food Science and Human Nutrition, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America; Center for Integrative Toxicology, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America.Department of Food Science and Human Nutrition, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America; Center for Integrative Toxicology, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America.Center for Integrative Toxicology, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America; Department of Microbiology and Molecular Genetics, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America.Division of Anatomic Pathology, Diagnostic Center for Population and Animal Health, Michigan State University, East Lansing, Michigan, United States of America.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24945254

Citation

Pestka, James J., et al. "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." PloS One, vol. 9, no. 6, 2014, pp. e100255.
Pestka JJ, Vines LL, Bates MA, et al. 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. PLoS ONE. 2014;9(6):e100255.
Pestka, J. J., Vines, L. L., Bates, M. A., He, K., & Langohr, I. (2014). 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. PloS One, 9(6), pp. e100255. doi:10.1371/journal.pone.0100255.
Pestka JJ, et al. 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. PLoS ONE. 2014;9(6):e100255. PubMed PMID: 24945254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Pestka,James J, AU - Vines,Laura L, AU - Bates,Melissa A, AU - He,Kaiyu, AU - Langohr,Ingeborg, Y1 - 2014/06/19/ PY - 2014/03/21/received PY - 2014/05/23/accepted PY - 2014/6/20/entrez PY - 2014/6/20/pubmed PY - 2015/3/13/medline SP - e100255 EP - e100255 JF - PloS one JO - PLoS ONE VL - 9 IS - 6 N2 - Mortality from systemic lupus erythematosus (SLE), a prototypical autoimmune disease, correlates with the onset and severity of kidney glomerulonephritis. There are both preclinical and clinical evidence that SLE patients may benefit from consumption of n-3 polyunsaturated fatty acids (PUFA) found in fish oil, but the mechanisms remain unclear. Here we employed the NZBWF1 SLE mouse model to compare the effects of dietary lipids on the onset and severity of autoimmune glomerulonephritis after consuming: 1) n-3 PUFA-rich diet containing docosahexaenoic acid-enriched fish oil (DFO), 2) n-6 PUFA-rich Western-type diet containing corn oil (CRN) or 3) n-9 monounsaturated fatty acid (MUFA)-rich Mediterranean-type diet containing high oleic safflower oil (HOS). Elevated plasma autoantibodies, proteinuria and glomerulonephritis were evident in mice fed either the n-6 PUFA or n-9 MUFA diets, however, all three endpoints were markedly attenuated in mice that consumed the n-3 PUFA diet until 34 wk of age. A focused PCR array was used to relate these findings to the expression of 84 genes associated with CD4+ T cell function in the spleen and kidney both prior to and after the onset of the autoimmune nephritis. n-3 PUFA suppression of autoimmunity in NZBWF1 mice was found to co-occur with a generalized downregulation of CD4+ T cell-related genes in kidney and/or spleen at wk 34. These genes were associated with the inflammatory response, antigen presentation, T cell activation, B cell activation/differentiation and leukocyte recruitment. Quantitative RT-PCR of representative affected genes confirmed that n-3 PUFA consumption was associated with reduced expression of CD80, CTLA-4, IL-10, IL-18, CCL-5, CXCR3, IL-6, TNF-α and osteopontin mRNAs in kidney and/or spleens as compared to mice fed n-6 PUFA or n-9 MUFA diets. Remarkably, many of the genes identified in this study are currently under consideration as biomarkers and/or biotherapeutic targets for SLE and other autoimmune diseases. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24945254/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_ L2 - http://dx.plos.org/10.1371/journal.pone.0100255 DB - PRIME DP - Unbound Medicine ER -