Simultaneous in vivo time course and dose response evaluation for TCDD-induced impairment of the LPS-stimulated primary IgM response.

Toxicological Sciences : an Official Journal of the Society of Toxicology
Colin M NorthNorbert E Kaminski

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent suppressor of humoral immunity but the specific molecular mechanisms responsible for immunosuppression by TCDD are poorly understood. In vivo and in vitro studies of the primary humoral IgM response demonstrated that the B cell is a sensitive cell type to modulation by TCDD. We hypothesized that in vivo administration of TCDD disrupts expression of transcription factors controlling B cell to plasma cell differentiation. Female C57BL6 mice were treated with a single dose of TCDD (3, 10, or 30 microg/kg) and/or vehicle (sesame oil). On day 4 post-TCDD administration mice were sensitized with 25 microg lipopolysacchride (LPS) by intraperitioneal injection to stimulate an immune response. Splenocytes were isolated on subsequent days following LPS, up to 3 days post-LPS, and the expression of IgM, XBP-1, PAX5, BCL-6, and Blimp-1 was assessed. TCDD treatment dose-dependently suppressed LPS-induced IgM antibody-forming cell number, which was correlated with decreased frequency of CD19+ CD138+ cells. Gene expression analysis revealed that TCDD caused a dose-dependent suppression of Igmicro chain, Igkappa chain, IgJ chain, XBP-1, and Blimp-1. TCDD also dose-dependently suppressed LP...Continue Reading

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Citations

Mar 30, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Colin M NorthNorbert E Kaminski
Sep 8, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·K Nadira De AbrewRussell S Thomas
Oct 19, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Courtney E W Sulentic, Norbert E Kaminski
Jan 8, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Emily A McClureJay I Goodman
Aug 2, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·V J SchulzR H H Pieters
Nov 12, 2009·Molecular Pharmacology·Iain A MurrayGary H Perdew
Sep 21, 2013·Chemico-biological Interactions·Hsiu-Min ChenYing-Jan Wang
Feb 21, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jiajun ZhouNorbert Kaminski
Sep 21, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert R HainesJeremy M Boss

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