Increased TGF-β and decreased oncogene expression by ω-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice

Gabriel Fernandes, Chandrasekar Bysani, Jaya T. Venkatraman, Vikram Tomar, Weiguo Zhao

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

This study was designed to investigate the mechanisms by which marine lipids rich in long chain ω-3 fatty acids inhibit autoimmune disease and prolong the survival rate in female (NZB/NZW) F1 (B/W) mice, an animal model for human SLE. Nutritionally adequate semipurified diets containing at 10% either corn oil (CO) or fish oil (FO) were fed from 1 mo of age and were monitored for proteinuria and survival. Proteinuria was detected earlier and became progressively severe in CO-fed mice. The average life span was significantly shortened by the CO diet (266.7 days ± 12.5), whereas FO extended the survival significantly (402.1 days ± 26.1; p < 0.001). A cross- sectional study at 6.5 mo of age revealed an increased proliferative response to T cell mitogens including bacterial superantigens and decreased serum anti-dsDNA Ab titers in the FO group compared with the CO group. Furthermore, splenocytes from the FO group when stimulated with Con A had higher IL-2 and lower IL-4 production similar to that of young (3.5 mo) mice. Flow cytometric analyses of splenocytes revealed lower Ig+, higher lymphocyte endothelial cell adhesion molecule-1, and lower Pgp-1+ cells within CD4+ and CD8+ subsets in FO-fed mice. Also, elevated IL-2 and IL-4 and significantly higher TGF-β1 and lower c-myc and c-ras mRNA expression and higher TGF-β1 and significantly lower c-Myc and c-Ha-Ras proteins were detected in spleens of FO-fed mice. Fatty acid analysis revealed significantly higher linoleic (18:2ω-6) and arachidonic (20:4ω-6) acid levels in splenocytes of the CO- fed group and higher eicosapentanoic (20:5ω-3) and docosahexanoic (22:6ω- 3) acid levels in the FO-fed group, indicating that changes in membrane fatty acid composition may contribute to the altered immune function and gene expression during the development of murine SLE.

Original languageEnglish (US)
Pages (from-to)5979-5987
Number of pages9
JournalJournal of Immunology
Volume152
Issue number12
StatePublished - Jun 15 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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