Morphine directs T cells toward TH2 differentiation

Sabita Roy, Sudha Balasubramanian, S. Sumandeep, Richard Charboneau, Jinghua Wang, Dean Melnyk, Greg J. Beilman, Rajan Vatassery, Roderick A. Barke

Research output: Contribution to journalArticle

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Abstract

Background. Failure of cell-mediated immunity is thought to increase the morbidity and mortality rates after trauma and major surgical procedures and to be the result, in part, of a redirection of CD4+ T cells toward TH2 differentiation. We tested the hypothesis that morphine treatment after injury promotes TH2 differentiation of precursor T cells through the μ-opioid receptor. Methods. Human peripheral blood mononuclear cells (PBMCs) or splenocytes from either wild type or μ-opioid receptor knock-out mice were treated in vitro with either vehicle or morphine and then stimulated with anti-CD3/anti-CD28. The supernatant was assayed for TH1 (interleukin-2 [IL-2], interferon γ [IFNγ]) and TH2 (IL-4, IL-5) cytokines (enzyme-linked immunosorbent assay). Morphine regulation of IL-4 transcription was investigated in PBMCs (IL-4 messenger RNA, nuclear factor of activated T-cells) and Jurkat T cells transfected with a murine IL-4 promoter-luciferase construct. Morphine-induced nuclear factor of activated T-cell (NFAT) binding was assayed with the electromobility shift assay in Jurkat T cells. Results. Morphine treatment of PBMCs decreases IL-2 and IFNγ and increases IL-4 and IL-5 as a function of morphine concentration. Morphine treatment in wild type splenocytes inhibited IFNγ and stimulated IL-4 protein synthesis. Changes in cytokine synthesis were abolished in μ-opioid receptor knockout mice. Morphine treatment increases IL-4 messenger RNA accumulation in PBMCs and increases IL-4 promoter activity in Jurkat T cells. Morphine increases NFAT nuclear protein binding to an NFAT DNA response element. Conclusions. We conclude that morphine treatment promotes TH2 differentiation through a μ-opioid receptor mechanism and that morphine treatment increases IL-4 transcription, in part, through an NFAT mechanism.

Original languageEnglish (US)
Pages (from-to)304-309
Number of pages6
JournalSurgery
Volume130
Issue number2
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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Morphine
Interleukin-4
T-Lymphocytes
NFATC Transcription Factors
Opioid Receptors
Jurkat Cells
Blood Cells
Interferons
Interleukin-5
Knockout Mice
Interleukin-2
Therapeutics
T-Lymphoid Precursor Cells
Cytokines
Messenger RNA
Wounds and Injuries
Response Elements
Nuclear Proteins
Luciferases
Protein Binding

ASJC Scopus subject areas

  • Surgery

Cite this

Roy, S., Balasubramanian, S., Sumandeep, S., Charboneau, R., Wang, J., Melnyk, D., ... Barke, R. A. (2001). Morphine directs T cells toward TH2 differentiation. Surgery, 130(2), 304-309. https://doi.org/10.1067/msy.2001.116033

Morphine directs T cells toward TH2 differentiation. / Roy, Sabita; Balasubramanian, Sudha; Sumandeep, S.; Charboneau, Richard; Wang, Jinghua; Melnyk, Dean; Beilman, Greg J.; Vatassery, Rajan; Barke, Roderick A.

In: Surgery, Vol. 130, No. 2, 01.01.2001, p. 304-309.

Research output: Contribution to journalArticle

Roy, S, Balasubramanian, S, Sumandeep, S, Charboneau, R, Wang, J, Melnyk, D, Beilman, GJ, Vatassery, R & Barke, RA 2001, 'Morphine directs T cells toward TH2 differentiation', Surgery, vol. 130, no. 2, pp. 304-309. https://doi.org/10.1067/msy.2001.116033
Roy S, Balasubramanian S, Sumandeep S, Charboneau R, Wang J, Melnyk D et al. Morphine directs T cells toward TH2 differentiation. Surgery. 2001 Jan 1;130(2):304-309. https://doi.org/10.1067/msy.2001.116033
Roy, Sabita ; Balasubramanian, Sudha ; Sumandeep, S. ; Charboneau, Richard ; Wang, Jinghua ; Melnyk, Dean ; Beilman, Greg J. ; Vatassery, Rajan ; Barke, Roderick A. / Morphine directs T cells toward TH2 differentiation. In: Surgery. 2001 ; Vol. 130, No. 2. pp. 304-309.
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abstract = "Background. Failure of cell-mediated immunity is thought to increase the morbidity and mortality rates after trauma and major surgical procedures and to be the result, in part, of a redirection of CD4+ T cells toward TH2 differentiation. We tested the hypothesis that morphine treatment after injury promotes TH2 differentiation of precursor T cells through the μ-opioid receptor. Methods. Human peripheral blood mononuclear cells (PBMCs) or splenocytes from either wild type or μ-opioid receptor knock-out mice were treated in vitro with either vehicle or morphine and then stimulated with anti-CD3/anti-CD28. The supernatant was assayed for TH1 (interleukin-2 [IL-2], interferon γ [IFNγ]) and TH2 (IL-4, IL-5) cytokines (enzyme-linked immunosorbent assay). Morphine regulation of IL-4 transcription was investigated in PBMCs (IL-4 messenger RNA, nuclear factor of activated T-cells) and Jurkat T cells transfected with a murine IL-4 promoter-luciferase construct. Morphine-induced nuclear factor of activated T-cell (NFAT) binding was assayed with the electromobility shift assay in Jurkat T cells. Results. Morphine treatment of PBMCs decreases IL-2 and IFNγ and increases IL-4 and IL-5 as a function of morphine concentration. Morphine treatment in wild type splenocytes inhibited IFNγ and stimulated IL-4 protein synthesis. Changes in cytokine synthesis were abolished in μ-opioid receptor knockout mice. Morphine treatment increases IL-4 messenger RNA accumulation in PBMCs and increases IL-4 promoter activity in Jurkat T cells. Morphine increases NFAT nuclear protein binding to an NFAT DNA response element. Conclusions. We conclude that morphine treatment promotes TH2 differentiation through a μ-opioid receptor mechanism and that morphine treatment increases IL-4 transcription, in part, through an NFAT mechanism.",
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AU - Roy, Sabita

AU - Balasubramanian, Sudha

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AU - Charboneau, Richard

AU - Wang, Jinghua

AU - Melnyk, Dean

AU - Beilman, Greg J.

AU - Vatassery, Rajan

AU - Barke, Roderick A.

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N2 - Background. Failure of cell-mediated immunity is thought to increase the morbidity and mortality rates after trauma and major surgical procedures and to be the result, in part, of a redirection of CD4+ T cells toward TH2 differentiation. We tested the hypothesis that morphine treatment after injury promotes TH2 differentiation of precursor T cells through the μ-opioid receptor. Methods. Human peripheral blood mononuclear cells (PBMCs) or splenocytes from either wild type or μ-opioid receptor knock-out mice were treated in vitro with either vehicle or morphine and then stimulated with anti-CD3/anti-CD28. The supernatant was assayed for TH1 (interleukin-2 [IL-2], interferon γ [IFNγ]) and TH2 (IL-4, IL-5) cytokines (enzyme-linked immunosorbent assay). Morphine regulation of IL-4 transcription was investigated in PBMCs (IL-4 messenger RNA, nuclear factor of activated T-cells) and Jurkat T cells transfected with a murine IL-4 promoter-luciferase construct. Morphine-induced nuclear factor of activated T-cell (NFAT) binding was assayed with the electromobility shift assay in Jurkat T cells. Results. Morphine treatment of PBMCs decreases IL-2 and IFNγ and increases IL-4 and IL-5 as a function of morphine concentration. Morphine treatment in wild type splenocytes inhibited IFNγ and stimulated IL-4 protein synthesis. Changes in cytokine synthesis were abolished in μ-opioid receptor knockout mice. Morphine treatment increases IL-4 messenger RNA accumulation in PBMCs and increases IL-4 promoter activity in Jurkat T cells. Morphine increases NFAT nuclear protein binding to an NFAT DNA response element. Conclusions. We conclude that morphine treatment promotes TH2 differentiation through a μ-opioid receptor mechanism and that morphine treatment increases IL-4 transcription, in part, through an NFAT mechanism.

AB - Background. Failure of cell-mediated immunity is thought to increase the morbidity and mortality rates after trauma and major surgical procedures and to be the result, in part, of a redirection of CD4+ T cells toward TH2 differentiation. We tested the hypothesis that morphine treatment after injury promotes TH2 differentiation of precursor T cells through the μ-opioid receptor. Methods. Human peripheral blood mononuclear cells (PBMCs) or splenocytes from either wild type or μ-opioid receptor knock-out mice were treated in vitro with either vehicle or morphine and then stimulated with anti-CD3/anti-CD28. The supernatant was assayed for TH1 (interleukin-2 [IL-2], interferon γ [IFNγ]) and TH2 (IL-4, IL-5) cytokines (enzyme-linked immunosorbent assay). Morphine regulation of IL-4 transcription was investigated in PBMCs (IL-4 messenger RNA, nuclear factor of activated T-cells) and Jurkat T cells transfected with a murine IL-4 promoter-luciferase construct. Morphine-induced nuclear factor of activated T-cell (NFAT) binding was assayed with the electromobility shift assay in Jurkat T cells. Results. Morphine treatment of PBMCs decreases IL-2 and IFNγ and increases IL-4 and IL-5 as a function of morphine concentration. Morphine treatment in wild type splenocytes inhibited IFNγ and stimulated IL-4 protein synthesis. Changes in cytokine synthesis were abolished in μ-opioid receptor knockout mice. Morphine treatment increases IL-4 messenger RNA accumulation in PBMCs and increases IL-4 promoter activity in Jurkat T cells. Morphine increases NFAT nuclear protein binding to an NFAT DNA response element. Conclusions. We conclude that morphine treatment promotes TH2 differentiation through a μ-opioid receptor mechanism and that morphine treatment increases IL-4 transcription, in part, through an NFAT mechanism.

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