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The Journal of Immunology, 2008, 181, 3057 -3066
Copyright © 2008 by The American Association of Immunologists, Inc.

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Cannabinoids Affect Dendritic Cell (DC) Potassium Channel Function and Modulate DC T Cell Stimulatory Capacity1

Paul W. Wacnik*,{dagger}, Katarina M. Luhr*, Russell H. Hill*, Hans-Gustaf Ljunggren{dagger}, Krister Kristensson* and Mattias Svensson2,{dagger}

* Department of Neuroscience, and {dagger} Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden

Cannabinoids affect diverse biological processes, including functions of the immune system. With respect to the immune system, anti-inflammatory and immunosuppressive effects of cannabinoids have been reported. Cannabinoids stimulate G protein-coupled cannabinoid receptors CB1 and CB2. These receptors are found primarily on neurons. However, they are also found on dendritic cells (DC), which are recognized for their critical role in initiating and maintaining immune responses. Therefore, DC are potential targets for cannabinoids. We report in this study that cannabinoids reduced the DC surface expression of MHC class II molecules as well as their capacity to stimulate T cells. In the nervous system, CB1 receptor signaling modulates K+ and Ca2+ channels. Interestingly, cannabinoid-treated DC also showed altered voltage-gated potassium (KV) channel function. We speculate that attenuation of KV channel function via CB1 receptor signaling in DC may represent one mechanism by which cannabinoids alter DC function.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work is supported by grants from the Swedish Research Council, the Swedish Foundation for Strategic Research, and the Karolinska Institutet. This work was also supported by Grants 4480 from the Swedish Research Council and FP-6-19090 from European Commission.

2 Address correspondence and reprint requests to Dr. Mattias Svensson, Center for Infectious Medicine, F59, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden. E-mail address: mattias.svensson{at}ki.se

3 Abbreviations used in this paper: KV, voltage-gated potassium; DC, dendritic cell; MHC-II, MHC class II; TEA, tetraethyl-ammonium; ACPA, arachidonylcyclopropylamide; PTX, pertussis toxin.







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