title: Acceleration of autoimmunity by organochlorine pesticides: a comparison of splenic B-cell effects of chlordecone and estradiol in (NZBxNZW)F1 mice.
abstract: 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.
authors.affiliation: Department of Pharmacology and Therapeutics, J. Hillis Miller Health Science Center, University of Florida, Gainesville 32610, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Roberts
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Butfiloski
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
authors.forename: Eric S
authors.initials: ES
authors.lastname: Sobel
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D007631:Chlordecone / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004958:Estradiol / Q000633:toxicity*; D005260:Female; D018858:Germinal Center / Q000187:drug effects / Q000473:pathology; D007306:Insecticides / Q000633:toxicity*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010052:Ovariectomy; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; C514936:CXCR4 protein, mouse; C513179:CXCR5 protein, mouse; D007306:Insecticides; D019253:Proto-Oncogene Proteins c-bcl-2; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1; C096712:antigen GL7; D018799:Intercellular Adhesion Molecule-1; D004958:Estradiol; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse; D007631:Chlordecone