The effect of the phytoestrogen coumestrol on the NZB/W F1 murine model of systemic lupus.
Coumestrol is a naturally occurring plant estrogen. As estrogen influences cellular and humoral immunity, and has known effects on murine models of lupus, we investigated the effect of coumestrol on disease expression in the NZB/W F1 mouse. Female NZB/W F1 mice were fed a "standard" rodent diet including soy proteins, a non-soy diet, or a non-soy diet with 0.01% coumestrol. Outcome measures included survival, autoantibody expression, immunoglobulin levels, proteinuria, renal histology and B cell immunohistochemistry, and renal mRNA expression. At 24 weeks, the treatment group had decreased prevalence of autoantibodies detected by immunofluorescence and less splenomegaly. At 39 weeks, the prevalence of autoantibodies was similar but the treatment group had less proteinuria. Overall, there was little effect of treatment on renal mRNA levels as assessed by gene array analysis, but functional ontology mapping revealed that genes encoding proteins involved in the immune response were most often affected. These results suggest that treatment with coumestrol may ameliorate some aspects of disease progression in this model of systemic autoimmunity.
Schoenroth
Leeanne J
LJ
Faculty of Medicine, HRB 410B, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
Hart
David A
DA
Pollard
K Michael
KM
Fritzler
Marvin J
MJ
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000187:drug effects; D002843:Chromatin / Q000276:immunology; D003375:Coumestrol / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007136:Immunoglobulins / Q000097:blood; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D020411:Oligonucleotide Array Sequence Analysis; D048789:Phytoestrogens / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D001323:Autoantibodies; D002843:Chromatin; D007136:Immunoglobulins; D048789:Phytoestrogens; D012333:RNA, Messenger; D003375:Coumestrol