Skip Navigation



ToxSci Advance Access published online on June 19, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm137
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
99/1/141    most recent
kfm137v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Wang, F.
Right arrow Articles by Sobel, E. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, F.
Right arrow Articles by Sobel, E. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Acceleration of Autoimmunity by Organochlorine Pesticides: A Comparison of Splenic B-Cell Effects of Chlordecone and Estradiol in (NZBxNZW)F1 Mice

Fei Wang*,¶, Stephen M. Roberts*,{dagger}, Edward J. Butfiloski{ddagger}, Laurence Morel§ and Eric S. Sobel{ddagger}

* Department of Pharmacology and Therapeutics {dagger} Department of Physiological Sciences {ddagger} Department of Medicine § Department of Pathology, Immunology and Laboratory Medicine, J. Hillis Miller Health Science Center, University of Florida, Gainesville, Florida, 32610, USA Present address: Occupational and Environmental Health Science, Merck & Co., Inc., Whitehouse Station, NJ, 08889, USA

Corresponding author: Dr. Stephen M. Roberts, Center for Environmental & Human Toxicology, Box 110885, University of Florida, Florida 32611, USA. Phone: (352) 392-4700 ext. 5500; Fax: (352) 392-4707, Email: smr{at}ufl.edu

Received March 22, 2007; revision received May 15, 2007; accepted May 17, 2007


  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 17ß-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 estrogen 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.

Key Words: autoimmunity; estrogen; chlordecone; spleen; splenocytes; systemic lupus erythematosus.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.