Wednesday, January 04, 2006

NIEHS Abstract

One of the most potent suppressors of the anti-sheep erythrocyte antibody forming cell (AFC) response is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The mechanism of TCDD-mediated suppression of the AFC response is known to be dependent on the aryl hydrocarbon receptor (AHR) and involves a disruption of B cell differentiation into plasma cells. Previous studies have shown that addition of Interferon gamma (IFNg) to in-vitro cultured mouse splenocytes prevented the suppression of AFC response caused by TCDD. To further characterize the effect of IFN on TCDD-mediated suppression of the AFC response other IFN forms were used in culture (IFN alpha or beta). To evaluate downstream AHR effects quantification of mRNA for Cyp1A1 and IgM heavy (IgH), kappa (IgK), and J (IgJ-chain) component chains was performed. Addition of 30nM TCDD to cultures caused Cyp1A1 mRNA increases as much as 38-fold over control, as well as significant decreases in the AFC response (58%), and decreased mRNA levels of IgH (37%), IgK (36%), and IgJ-chain (68%). Co-treatment of splenocytes with TCDD and 100U/mL IFNg prevented suppression of the AFC response. mRNA levels of Igh, Igk, and Igj from splenocytes cocultured with TCDD and IFNg returned to near control values. TCDD-mediated induction of CYP1A1 was attenuated by as much as 50% with IFNg. Treatment with IFNa or IFNb did not alter the effect of TCDD on the AFC response. Additionally, for IFNg to reverse the effect of TCDD on the AFC response it must be added to the culture within two hours of TCDD and antigen.