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Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Cannabinoid Treatment Suppresses the T-Helper Cell-Polarizing Function of Mouse Dendritic Cells Stimulated with Legionella pneumophila Infection

Tangying Lu, Cathy Newton, Izabella Perkins, Herman Friedman and Thomas W. Klein
Journal of Pharmacology and Experimental Therapeutics October 2006, 319 (1) 269-276; DOI: https://doi.org/10.1124/jpet.106.108381
Tangying Lu
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Cathy Newton
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Izabella Perkins
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Herman Friedman
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Thomas W. Klein
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Abstract

Marijuana cannabinoids, such as δ-9-tetrahydrocannabinoid (THC), suppress type 1 T-helper 1 (Th1) immunity in a variety of models, including infection with the intracellular pathogen Legionella pneumophila (Lp). To examine the cellular mechanism of this effect, bone marrow-derived dendritic cells (DCs) were purified from BALB/c mice and studied following infection and drug treatment. DCs infected in vitro with Lp were able to protect mice when injected prior to a lethal Lp infection; however, the immunization potential of the Lp-loaded cells along with Th1 cytokine production was attenuated by THC treatment at the time of in vitro infection. In addition, THC-treated and Lp-loaded DCs were poorly stimulated in culture-primed splenic CD4+ T cells to produce interferon-γ; however, this stimulating deficiency was reversed by adding recombinant interleukin (IL)-12p40 protein to the cultures. Moreover, THC treatment inhibited the expression of DC maturation markers, such as major histocompatibility complex class II and costimulatory molecules CD86 and CD40 as determined by flow cytometry and suppressed the Notch ligand, Del-ta4, as determined by reverse transcription-polymerase chain reaction. However, THC treatment did not affect other DC functions, such as intracellular killing of Lp, determined by colony-forming unit counts of bacteria, and Lp-induced apoptosis, determined by annexin V staining. In conclusion, the data suggest that THC inhibits Th1 activation by targeting essential DC functions, such as IL-12p40 secretion, maturation, and expression of costimulatory and polarizing molecules.

Footnotes

  • This work was supported by National Institutes of Health Grants DA03646, DA10683, and AI45169.

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

  • doi:10.1124/jpet.106.108381.

  • ABBREVIATIONS: Th1, type 1 T-helper cell; Th2, type 2-T helper cell; THC, δ-9-tetrahydrocannabinol; DCs, dendritic cells; Lp, Legionella pneumophila; LpDC, Lp-loaded DC; IFN-γ, interferon-γ; IL, interleukin; MHC, major histocompatibility complex; DMSO, dimethyl sulfoxide; GM-CSF, granulocyte-macrophage colony-stimulating factor; PBS, phosphate-buffered saline; CFU, colony-forming unit; mAb, monoclonal antibody; ELISA, enzyme-linked immunosorbent assay; i.v., intravenous; bp, base pair; PE, phycoerythrin.

    • Received May 25, 2006.
    • Accepted July 10, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 387 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 387, Issue 1
1 Oct 2023
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Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Cannabinoid Treatment Suppresses the T-Helper Cell-Polarizing Function of Mouse Dendritic Cells Stimulated with Legionella pneumophila Infection

Tangying Lu, Cathy Newton, Izabella Perkins, Herman Friedman and Thomas W. Klein
Journal of Pharmacology and Experimental Therapeutics October 1, 2006, 319 (1) 269-276; DOI: https://doi.org/10.1124/jpet.106.108381

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Research ArticleINFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Cannabinoid Treatment Suppresses the T-Helper Cell-Polarizing Function of Mouse Dendritic Cells Stimulated with Legionella pneumophila Infection

Tangying Lu, Cathy Newton, Izabella Perkins, Herman Friedman and Thomas W. Klein
Journal of Pharmacology and Experimental Therapeutics October 1, 2006, 319 (1) 269-276; DOI: https://doi.org/10.1124/jpet.106.108381
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