Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Aryl Hydrocarbon Receptor Activation in Hematopoietic Stem/Progenitor Cells Alters Cell Function and Pathway-Specific Gene Modulation Reflecting Changes in Cellular Trafficking and Migration

Fanny L. Casado, Kameshwar P. Singh and Thomas A. Gasiewicz
Molecular Pharmacology October 2011, 80 (4) 673-682; DOI: https://doi.org/10.1124/mol.111.071381
Fanny L. Casado
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kameshwar P. Singh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas A. Gasiewicz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the Per-ARNT-Sim family of proteins. These proteins sense molecules and stimuli from the cellular/tissue environment and initiate signaling cascades to elicit appropriate cellular responses. Recent literature reports suggest an important function of AhR in hematopoietic stem cell (HSC) biology. However, the molecular mechanisms by which AhR signaling regulates HSC functions are unknown. In previous studies, we and others reported that treatment of mice with the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) compromises the competitive reconstitution of bone marrow (BM) cells into irradiated host animals. Additional studies indicated a requirement for AhR in hematopoietic cells and not marrow microenvironment cells. In this study, we tested the hypothesis that TCDD-mediated phenotypic and functional changes of HSCs are a result of changes in gene expression that disrupt stem cell numbers and/or their migration. TCDD treatment to mice increased the numbers of phenotypically defined HSCs in BM. These cells showed compromised migration to the BM in vivo and to the chemokine CXCL12 in vitro, as well as increased expression of the leukemia-associated receptors CD184 (CXCR4) and CD44. Gene expression profiles at 6 and 12 h after exposure were consistent with the phenotypic and functional changes observed. The expressions of Scin, Nqo1, Flnb, Mmp8, Ilf9, and Slamf7 were consistently altered. TCDD also disrupted expression of other genes involved in hematological system development and function including Fos, JunB, Egr1, Ptgs2 (Cox2), and Cxcl2. These data support a molecular mechanism for an AhR ligand to disrupt the homeostatic cell signaling of HSCs that may promote altered HSC function.

Footnotes

  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • This work was funded by the National Institutes of Health National Institute of Environmental Health Sciences [Grants ES01247, ES07026, ES04862, ES016606].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.111.071381.

  • ABBREVIATIONS:

    AhR
    aryl hydrocarbon receptor
    TCDD
    2,3,7,8-tetrachlorodibenzo-p-dioxin
    BM
    bone marrow
    HSC
    hematopoietic stem cell
    URMC
    University of Rochester Medical Center
    7AAD
    7-amino-actinomycin D
    LSK
    lineage-depleted, Sca-1+ and c-kit+
    APC
    allophycocyanin
    FITC
    fluorescein isothiocyanate
    IL
    interleukin
    PBS
    phosphate-buffered saline
    CXCL12
    chemokine (C-X-C motif) ligand 12
    PE
    phycoerythrin
    RT2
    real-time reverse transcription
    PCR
    polymerase chain reaction
    IPA
    Ingenuity Pathway Analysis
    ANOVA
    analysis of variance
    SLAM
    signaling lymphocyte activation molecule
    NF-κB
    nuclear factor-κB.

  • Received January 25, 2011.
  • Accepted July 26, 2011.
  • Copyright © 2011 The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 80 (4)
Molecular Pharmacology
Vol. 80, Issue 4
1 Oct 2011
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Aryl Hydrocarbon Receptor Activation in Hematopoietic Stem/Progenitor Cells Alters Cell Function and Pathway-Specific Gene Modulation Reflecting Changes in Cellular Trafficking and Migration
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

AhR Activation Alters Migration of Hematopoietic Stem Cells

Fanny L. Casado, Kameshwar P. Singh and Thomas A. Gasiewicz
Molecular Pharmacology October 1, 2011, 80 (4) 673-682; DOI: https://doi.org/10.1124/mol.111.071381

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

AhR Activation Alters Migration of Hematopoietic Stem Cells

Fanny L. Casado, Kameshwar P. Singh and Thomas A. Gasiewicz
Molecular Pharmacology October 1, 2011, 80 (4) 673-682; DOI: https://doi.org/10.1124/mol.111.071381
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
  • Benzbromarone relaxes airway smooth muscle via BK activation
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics