Increased TGF-beta and decreased oncogene expression by omega-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice.
This study was designed to investigate the mechanisms by which marine lipids rich in long chain omega-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-beta 1 and lower c-myc and c-ras mRNA expression and higher TGF-beta 1 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 (18:2 omega-6) and arachidonic (20:4 omega-6) acid levels in splenocytes of the CO-fed group and higher eicosapentaenoic (20:5 omega-3) and docosahexanoic (22:6 omega-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.
Fernandes
G
G
Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
Bysani
C
C
Venkatraman
J T
JT
Tomar
V
V
Zhao
W
W
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D009857:Oncogenes / Q000187:drug effects; D011507:Proteinuria / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics*
D000974:Antibodies, Antinuclear; D015525:Fatty Acids, Omega-3; D007376:Interleukin-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4