Abstract/Details

Characterization of transcriptional changes in blood leukocytes following acute morphine-induced immunosuppression


2004 2004

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Abstract (summary)

Administration of opioids to both humans and animal models results in significant alterations in immune system responsiveness. While the majority of studies have focused on phenotypic changes in immune cells following acute and chronic morphine administration, few studies have determined whether alterations in gene expression profiles accompany these effects. To address this question, rats were treated with either morphine (20 mg/kg) or saline, and changes in gene expression and function in blood leukocytes were examined. Within two hours, morphine administration resulted in a number of genes being regulated including genes involved in signal transduction, structure, enzymes, transcription, receptors, metabolism, proliferation and protein trafficking. However, the most striking and immunologically relevant decrease was observed in blood leukocyte expression of the major histocompatibility complex class II (MHC II RT1. B beta) (−3.27 fold) and related molecules including the MHC II invariant chain (−2.73 fold). These changes in gene expression were accompanied by a significant decrease in surface MHC II RT1. B beta protein expression (20%), specifically on B lymphocytes. Morphine administration also inhibited IL-4 induced up-regulation of MHC II RT1. B beta cell surface expression on B lymphocytes but not on monocytes following both a 24 and 48 hour stimulation. This effect was attenuated by a PKA inhibitor but was insensitive to a PKC inhibitor. Furthermore, experiments demonstrated that STAT6 activity is decreased following a 2 hour in vivo morphine treatment as measured by CD23 expression. In vitro morphine and corticosterone did not effect the ability of B lymphocytes to up-regulate MHC II following IL-4 stimulation indicating that morphine and corticosterone do not directly play a role in MHC II mediated immunosuppression. The suppression of MHC II RT 1. B beta following in vivo morphine treatment resulted in an inability of the B lymphocyte to bind to SEB and the T cell receptor causing a decrease in T cell activity as measured by CD25 expression. We propose that the inability of B lymphocytes to up-regulate key immune proteins such as the MHC II molecule following exposure to antigen-induced cytokine production may account for the increase in the susceptibility of bacterial and viral infections.

Indexing (details)


Subject
Molecular biology;
Pharmacology;
Immunology
Classification
0307: Molecular biology
0419: Pharmacology
0982: Immunology
Identifier / keyword
Health and environmental sciences; Biological sciences; Blood leukocytes; Immunosuppression; MHC class II; Morphine-induced; Transcriptional changes
Title
Characterization of transcriptional changes in blood leukocytes following acute morphine-induced immunosuppression
Author
Beagles, Karen Elizabeth
Number of pages
190
Publication year
2004
Degree date
2004
School code
0544
Source
DAI-B 65/10, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780496101092, 0496101099
Advisor
Bayer, Barbara M.
University/institution
Georgetown University Medical Center
University location
United States -- District of Columbia
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3150482
ProQuest document ID
305081703
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305081703/abstract
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