Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown previously that chronic treatment with relatively low doses of chlordecone accelerates the development of systemic lupus erythematosus (SLE) in ovariectomized female (NZBxNZW) F(1) mice. In this study, the effect of chronic chlordecone treatment on SLE was evaluated in ovary-intact female (NZBxNZW) F(1) mice, as well as in female mice from a strain that is not lupus-prone, BALB/c. Chlordecone was administered chronically via implanted sustained-release pellets, and mice were monitored over time for the appearance of elevated autoantibodies (anti-dsDNA and anti-chromatin) and for the development of renal impairment, both indicators of SLE. Chlordecone treatment in (NZBxNZW) F(1) mice shortened significantly the time to onset of elevated autoantibody titers and renal disease in a dose-related manner. The doses required to produce this effect were similar to those observed previously to accelerate SLE development in ovariectomized females. Treatment of female BALB/c mice with chlordecone for up to one year did not produce elevated autoantibody titers or renal disease, suggesting an inability of chlordecone to cause a break in tolerance in this strain. These observations confirm the ability of chronic chlordecone to influence SLE, but demonstrate the importance of genetic background for this effect.
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PMID:Comparison of chlordecone effects on autoimmunity in (NZBxNZW) F(1) and BALB/c mice. 1630 13

The weakly estrogenic organochlorine pesticide chlordecone can accelerate the development of systemic lupus erythematosus (SLE) in ovariectomized (NZBxNZW)F1 mice, with a shortened time to appearance of autoantibodies and disease similar to that produced by treatment with the sex hormone 17beta-estradiol (E2). It is unclear whether chlordecone and E2 share the same pathways in mediating this effect. The effects of chlordecone and E2 treatment on splenic germinal center (GC) and marginal zone B cells were examined. Both chlordecone and E2 activated splenic B cells and enhanced GC reactions, as shown by upregulated protein expression of GL7, CXCR5, and CXCR4. Both treatments increased B-cell bcl-2 and shp-1 gene expression and enhanced ICAM-1 and VCAM-1 protein levels in GC B cells. Chlordecone reduced total B cell and GC B-cell apoptosis without affecting proliferation, another feature shared by E2 treatment. However, chlordecone treatment did not alter the composition of splenic B-cell subsets in marked contrast to the decrease in transitional B cells and increase in marginal zone B cells seen in E2-treated mice. The differences in effects between chlordecone and E2 indicate that chlordecone is not functioning simply as an estrogen mimic with respect to effects on the immune system. Similarities in the effects of chlordecone and E2 on specific immune functions, such as diminished apoptosis in GC B cells, may provide valuable clues regarding key events in the acceleration of autoimmunity by E2, chlordecone, and other agents.
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PMID:Acceleration of autoimmunity by organochlorine pesticides: a comparison of splenic B-cell effects of chlordecone and estradiol in (NZBxNZW)F1 mice. 1757 64