GSBS Student Publications

Title

3,4-Dichloropropionanilide (DCPA) inhibits T-cell activation by altering the intracellular calcium concentration following store depletion

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Microbiology

Date

2-19-2008

Document Type

Article

Medical Subject Headings

Anilides; Animals; Calcium; Cell Nucleus; Female; Homeostasis; Humans; Interleukin-2; Jurkat Cells; Lymphocyte Activation; Membrane Potentials; Mice; Mice, Inbred BALB C; NFATC Transcription Factors; Protein Transport; Spectrometry, Fluorescence; T-Lymphocytes; Thapsigargin

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Stimulation of T cells through the T-cell receptor results in the activation of a series of signaling pathways that leads to the secretion of interleukin (IL)-2 and cell proliferation. Influx of calcium (Ca(2+)) from the extracellular environment, following internal Ca(2+) store depletion, provides the elevated and sustained intracellular calcium concentration ([Ca(2+)](i)) critical for optimal T-cell activation. Our laboratory has documented that exposure to the herbicide 3,4-dichloropropionanilide (DCPA) inhibits intracellular signaling events that have one or more Ca(2+) dependent steps. Herein we report that DCPA attenuates the normal elevated and sustained [Ca(2+)](i) that follows internal store depletion in the human leukemic Jurkat T cell line and primary mouse T cells. DCPA did not alter the depletion of internal Ca(2+) stores when stimulated by anti-CD3 or thapsigargin demonstrating that early inositol 1,4,5-triphosphate-mediated signaling and depletion of Ca(2+) stores were unaffected. 2-Aminoethyldiphenol borate (2-APB) is known to alter the store-operated Ca(2+) (SOC) influx that follows Ca(2+) store depletion. Exposure of Jurkat cells to either DCPA or 50 microM 2-APB attenuated the increase in [Ca(2+)](i) following thapsigargin or anti-CD3 induced store depletion in a similar manner. At low concentrations, 2-APB enhances SOC influx but this enhancement is abrogated in the presence of DCPA. This alteration in [Ca(2+)](i), when exposed to DCPA, significantly reduces nuclear levels of nuclear factor of activated T cells (NFAT) and IL-2 secretion. The plasma membrane polarization profile is not altered by DCPA exposure. Taken together, these data indicate that DCPA inhibits T-cell activation by altering Ca(2+) homeostasis following store depletion.

Rights and Permissions

Citation: Toxicol Sci. 2008 May;103(1):97-107. Epub 2008 Feb 14. Link to article on publisher's site

DOI of Published Version

10.1093/toxsci/kfn031

Related Resources

Link to Article in PubMed

Journal Title

Toxicological sciences : an official journal of the Society of Toxicology

PubMed ID

18281253