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Title: Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in altered thymocyte development

Abstract

Cadmium (Cd) is both an environmental pollutant and a component of cigarette smoke. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports in the literature of immunomodulatory effects of prenatal exposure to Cd. The sonic hedgehog (Shh) and Wnt/beta-catenin pathways are required for thymocyte maturation. Several studies have demonstrated that Cd exposure affects these pathways in different organ systems. This study was designed to investigate the effect of prenatal Cd exposure on thymocyte development, and to determine if these effects were linked to dysregulation of Shh and Wnt/beta-catenin pathways. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose (10 ppm) of Cd throughout pregnancy and effects on the thymus were assessed on the day of birth. Thymocyte phenotype was determined by flow cytometry. A Gli:luciferase reporter cell line was used to measure Shh signaling. Transcription of target genes and translation of key components of both signaling pathways were assessed using real-time RT-PCR and western blot, respectively. Prenatal Cd exposure increased the number of CD4{sup +} cells and a subpopulation of double-negative cells (DN; CD4{sup -}CD8{sup -}), DN4 (CD44{sup -}CD25{sup -}). Shh and Wnt/beta-catenin signaling were both decreased in the thymus.more » Target genes of Shh (Patched1 and Gli1) and Wnt/beta-catenin (c-fos, and c-myc) were affected differentially among thymocyte subpopulations. These findings suggest that prenatal exposure to Cd dysregulates two signaling pathways in the thymus, resulting in altered thymocyte development.« less

Authors:
; ;  [1];  [2]
  1. Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, PO Box 9177, West Virginia University, Morgantown, WV 26506-9177 (United States)
  2. Department of Animal and Nutritional Sciences, Davis College of Agriculture, Forestry and Consumer Sciences, West Virginia University, Morgantown, WV 26506 (United States)
Publication Date:
OSTI Identifier:
21344834
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 242; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2009.09.023; PII: S0041-008X(09)00415-3; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CADMIUM; DOSES; LUCIFERASE; MICE; PREGNANCY; PRENATAL EXPOSURE; THYMUS; TOBACCO SMOKES; TOXICITY; AEROSOLS; ANIMALS; BODY; COLLOIDS; DISPERSIONS; ELEMENTS; ENZYMES; LYMPHATIC SYSTEM; MAMMALS; METALS; ORGANIC COMPOUNDS; ORGANS; OXIDASES; OXIDOREDUCTASES; PROTEINS; RESIDUES; RODENTS; SMOKES; SOLS; VERTEBRATES

Citation Formats

Hanson, Miranda L, Brundage, Kathleen M, Schafer, Rosana, Tou, Janet C, and Barnett, John B., E-mail: jbarnett@hsc.wvu.ed. Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in altered thymocyte development. United States: N. p., 2010. Web. doi:10.1016/j.taap.2009.09.023.
Hanson, Miranda L, Brundage, Kathleen M, Schafer, Rosana, Tou, Janet C, & Barnett, John B., E-mail: jbarnett@hsc.wvu.ed. Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in altered thymocyte development. United States. https://doi.org/10.1016/j.taap.2009.09.023
Hanson, Miranda L, Brundage, Kathleen M, Schafer, Rosana, Tou, Janet C, and Barnett, John B., E-mail: jbarnett@hsc.wvu.ed. 2010. "Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in altered thymocyte development". United States. https://doi.org/10.1016/j.taap.2009.09.023.
@article{osti_21344834,
title = {Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in altered thymocyte development},
author = {Hanson, Miranda L and Brundage, Kathleen M and Schafer, Rosana and Tou, Janet C and Barnett, John B., E-mail: jbarnett@hsc.wvu.ed},
abstractNote = {Cadmium (Cd) is both an environmental pollutant and a component of cigarette smoke. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports in the literature of immunomodulatory effects of prenatal exposure to Cd. The sonic hedgehog (Shh) and Wnt/beta-catenin pathways are required for thymocyte maturation. Several studies have demonstrated that Cd exposure affects these pathways in different organ systems. This study was designed to investigate the effect of prenatal Cd exposure on thymocyte development, and to determine if these effects were linked to dysregulation of Shh and Wnt/beta-catenin pathways. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose (10 ppm) of Cd throughout pregnancy and effects on the thymus were assessed on the day of birth. Thymocyte phenotype was determined by flow cytometry. A Gli:luciferase reporter cell line was used to measure Shh signaling. Transcription of target genes and translation of key components of both signaling pathways were assessed using real-time RT-PCR and western blot, respectively. Prenatal Cd exposure increased the number of CD4{sup +} cells and a subpopulation of double-negative cells (DN; CD4{sup -}CD8{sup -}), DN4 (CD44{sup -}CD25{sup -}). Shh and Wnt/beta-catenin signaling were both decreased in the thymus. Target genes of Shh (Patched1 and Gli1) and Wnt/beta-catenin (c-fos, and c-myc) were affected differentially among thymocyte subpopulations. These findings suggest that prenatal exposure to Cd dysregulates two signaling pathways in the thymus, resulting in altered thymocyte development.},
doi = {10.1016/j.taap.2009.09.023},
url = {https://www.osti.gov/biblio/21344834}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 242,
place = {United States},
year = {Fri Jan 15 00:00:00 EST 2010},
month = {Fri Jan 15 00:00:00 EST 2010}
}