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Temporal variation in CB2R levels following T lymphocyte activation : evidence that cannabinoids modulate CXCL12-induced chemotaxis.

Coopman, Karen and Smith, Laura D. and Wright, Karen L. and Ward, Stephen G. (2007) Temporal variation in CB2R levels following T lymphocyte activation : evidence that cannabinoids modulate CXCL12-induced chemotaxis. International Immunopharmacology, 7 (3). pp. 360-371. ISSN 1567-5769

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Abstract

Cannabinoids have long been proposed to affect the immune system, especially as one of the cannabinoid receptors, the cannabinoid receptor-2 (CB2R) has been found almost exclusively on immune cells. Here, using human in vitro activated peripheral blood-derived T lymphocytes we investigated the long-term changes in cannabinoid receptor protein expression following cellular activation and the effects of cannabinoids on migration. We report that resting T lymphocytes do not detectably express either the cannabinoid receptor-1 (CB1R) or CB2R at the protein level. However, CB2R protein expression is upregulated in a biphasic manner in T lymphocytes following activation by superantigen. The cannabinoids 2-AG and JWH-133 were found to elicit activation of downstream biochemical effectors (as assessed by the phosphorylation of the ERK1/2 MAP kinases). Neither 2-AG nor JWH-133 induced chemotaxis in day 5 activated T lymphocytes, when receptor expression was at its highest. Interestingly, both 2-AG and JWH-133 inhibited CXCL12-induced chemotaxis, suggesting a modulatory role for cannabinoids in activated T lymphocytes. Keywords: Cannabinoid; Receptors; T lymphocyte; Migration Abbreviations: 2-AG, 2-arachidonoylglycerol; AEA, arachidonoylethanolamide; CB1R, cannabinoid receptor-1; CB2R, cannabinoid receptor-2; ERK, extracellular signal-regulated kinase; FAAH, fatty acid amide hyrdrolase; GPCR, G-protein coupled receptor; MAGL, monoacylglycerol lipase; PBMC, peripheral blood mononuclear cell; PMA, phorbyl 13-myristate 12-acetate; PI3K, phosphoinositide 3-kinase; PTX, pertussis toxin; SEB, Staphyloccocal enterotoxin B; WCL, whole cell lysate.

Item Type: Article
Journal or Publication Title: International Immunopharmacology
Subjects: R Medicine > RM Therapeutics. Pharmacology
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 40887
Deposited By: Mr Richard Ingham
Deposited On: 16 Jun 2011 09:45
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 18:06
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/40887

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