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Chem Res Toxicol. 2018 Nov 19;31(11):1248-1259. doi: 10.1021/acs.chemrestox.8b00225. Epub 2018 Oct 30.

Characterizing Serpinb2 as a Modulator of TCDD-Induced Suppression of the B Cell.

Author information

1
Department of Biochemistry and Molecular Biology , Michigan State University , East Lansing , Michigan 48824 , United States.
2
Institute for Integrative Toxicology , Michigan State University , East Lansing , Michigan 48824 , United States.
3
Interdisciplinary Program in Toxicology , Texas A&M University , College Station , Texas 77843 , United States.
4
Department of Pharmacology and Toxicology , Michigan State University , East Lansing , Michigan 48824 , United States.

Abstract

2,3,7,8-Tetrachlordibenzo- p-dioxin (TCDD) is an environmental pollutant that can cause various toxic effects, including chloracne, metabolic syndrome, and immune suppression. Most of the toxicity associated with TCDD is mediated through activation of the aryl hydrocarbon receptor (AHR). Recent research has suggested the presence of a wide-range of interindividual variability in TCDD-mediated suppression of the Immunoglobulin-M (IgM) response across the human population. In an attempt to identify putative modifiers of AHR-mediated immunosuppression beyond the AHR, B cells were isolated from a panel of genetically diverse mouse strain to scan for modulators that drive interstrain differences in TCDD-mediated suppression of the IgM response. Results implicated a region of mouse Chromosome 1 near a gene encoding serine peptidase inhibitor, clade B, member 2 ( Serpinb2) whose human ortholog is plasminogen activator inhibitor 2 (PAI2). Further downstream analyses indicated that Serpinb2 is dysregulated by TCDD and, furthermore, that B cells from Serpinb2 -/- mice are significantly more sensitive to TCDD-mediated suppression as compared to littermate controls. This study suggests a protective role of Serpinb2 within TCDD-mediated immunosuppression and, furthermore, a novel function of Serpinb2-related activity in the IgM response.

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