Morphine withdrawal inhibits IL-12 induction in a macrophage cell line through a mechanism that involves cAMP

Jennifer Kelschenbach, Jana Ninkovic, Jinghua Wang, Anitha Krishnan, Richard Charboneau, Roderick A. Barke, Sabita Roy

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

There are very few studies that examine the effects that morphine withdrawal has on immune functioning, and of these even fewer describe the mechanisms by which withdrawal brings about these changes. Our previous work demonstrated that morphine withdrawal contributed to Th cell differentiation by biasing cells toward the Th2 lineage. A major finding from these studies was that IL-12 was decreased following withdrawal, and it was concluded that this decrease may be a mechanism by which morphine withdrawal is mediating Th2 polarization. Therefore, it was the aim of the current studies to develop an in vitro model to examine the process of morphine withdrawal and to understand the signaling mechanisms that withdrawal may use to effect IL-12 production through the use of this model. It was demonstrated and concluded that morphine withdrawal may be effecting IL-12 production by increasing cAMP levels, which activates protein kinase A. Protein kinase A activation then prevents the phosphorylation and subsequent degradation of IκB, which in turn prevents translocation of the NF-κB p65 subunit to the nucleus to transactivate the IL-12 p40 gene, ultimately resulting in decreased IL-12 production following LPS stimulation.

Original languageEnglish (US)
Pages (from-to)3670-3679
Number of pages10
JournalJournal of Immunology
Volume180
Issue number6
DOIs
StatePublished - Mar 15 2008
Externally publishedYes

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Interleukin-12
Morphine
Macrophages
Cell Line
Cyclic AMP-Dependent Protein Kinases
Th2 Cells
Cell Differentiation
Phosphorylation
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Morphine withdrawal inhibits IL-12 induction in a macrophage cell line through a mechanism that involves cAMP. / Kelschenbach, Jennifer; Ninkovic, Jana; Wang, Jinghua; Krishnan, Anitha; Charboneau, Richard; Barke, Roderick A.; Roy, Sabita.

In: Journal of Immunology, Vol. 180, No. 6, 15.03.2008, p. 3670-3679.

Research output: Contribution to journalArticle

Kelschenbach, Jennifer ; Ninkovic, Jana ; Wang, Jinghua ; Krishnan, Anitha ; Charboneau, Richard ; Barke, Roderick A. ; Roy, Sabita. / Morphine withdrawal inhibits IL-12 induction in a macrophage cell line through a mechanism that involves cAMP. In: Journal of Immunology. 2008 ; Vol. 180, No. 6. pp. 3670-3679.
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