Skip Navigation



ToxSci Advance Access published online on October 22, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn223
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
107/1/85    most recent
kfn223v1
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 North, C. M.
Right arrow Articles by Kaminski, N. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by North, C. M.
Right arrow Articles by Kaminski, N. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

TCDD-Mediated Suppression of the in vitro Anti-Sheep Erythrocyte IgM Antibody Forming Cell Response is Reversed by Interferon Gamma

Colin M. North*,§,||, Byung-Sam Kim{dagger},||, Neil Snyder{ddagger}, Robert B. Crawford*,§, Michael P. Holsapple and Norbert E. Kaminski*,§,|||

* Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, 48824 USA {dagger} Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan, Ulsan, South Korea {ddagger} Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA § Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA ILSI Health and Environmental Sciences Institute, Washington, DC, 20005 USA

||| To who correspondence should be addressed at 315 National Food Safety & Toxicology Center, Michigan State University, East Lansing, MI 48824, USA

Received August 1, 2008; revision received October 7, 2008; accepted October 9, 2008


  Abstract

Suppression of humoral immune responses by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been well established to require the aryl hydrocarbon receptor; however, the downstream mechanisms for this immunotoxic response remain poorly understood. Based on evidence demonstrating that primary hepatocytes pretreated with interferon-gamma (IFN{gamma}) exhibited decreased induction of cytochrome P450 1A1 (CYP1A1) by TCDD, and that serum factors alter the sensitivity of the in vitro T cell-dependent IgM antibody forming cell (AFC) response, it was hypothesized that IFN{gamma} attenuates suppression of humoral immune responses by TCDD. In fact, concomitant addition of IFN{gamma} (100 U/mL) produced a concentration-related attenuation of TCDD-mediated suppression of the anti-sRBC IgM AFC response. Time of addition studies performed by adding 100 U/mL IFN{gamma} at 0, 1, 2, 4, 12, 24, 48, and 72 h post-TCDD showed that suppression of the AFC response was prevented only when IFN{gamma} was added within 2 h of TCDD treatment. mRNA levels of the IgM components, immunoglobulin {kappa} light chain, immunoglobulin µ heavy chain, and immunoglobulin J-chain were significantly decreased by TCDD treatment, an effect that was completely reversed by IFN{gamma} (100 U/mL) cotreatment. Further studies showed that IFN{alpha}, IFNβ, and IFN{gamma} significantly attenuate TCDD-induced increases in CYP1A1 mRNA levels to varying degrees, but concentrations as high as 1000 U/mL of type I IFNs, did not reverse the effect of TCDD on the anti-sheep erythrocyte (anti-sRBC) IgM AFC response. In summary, IFN{gamma} prevents TCDD-mediated suppression of the IgM AFC response in a concentration- and time-related manner by altering transcriptional effects associated with TCDD treatment.

Key Words: TCDD; immunotoxicology; IgM; in vitro; IFN{gamma}.

|| These authors contributed equally to this work


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.