Temporal variation in CB2R levels following T lymphocyte activation: evidence that cannabinoids modulate CXCL12-induced chemotaxis.
Cannabinoids have long been proposed to affect the immune system, especially as one of the cannabinoid receptors, the cannabinoid receptor-2 (CB(2)R) 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 (CB(1)R) or CB(2)R at the protein level. However, CB(2)R 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.
Coopman
Karen
K
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, U.K.
Smith
Laura D
LD
Wright
Karen L
KL
Ward
Stephen G
SG
D000328:Adult; D000581:Amidohydrolases / Q000235:genetics; D001095:Arachidonic Acids / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D063388:Endocannabinoids; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D008994:Monoacylglycerol Lipases / Q000235:genetics; D010766:Phosphorylation; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D043885:Receptor, Cannabinoid, CB2 / Q000032:analysis* / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D002186:Cannabinoids; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D063388:Endocannabinoids; D048049:Extracellular Signal-Regulated MAP Kinases; D005989:Glycerides; D008994:Monoacylglycerol Lipases; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C515255:CXCL12 protein, human; C094503:glyceryl 2-arachidonate; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC; C078814:anandamide